Is it worth going to Portofino third week of Oct?

Worth is always in the eye of the beholder. I don't know. It is an interesting port, very pretty and picturesque but it is small. We enjoyed our day. I am not sure I would make a huge effort to visit but I think it is worth it. We have never encountered much rain in Oct. More rain in April and May.

Thank you for the response.

It is a very tiny town. Both times we were in Santa Margherita Ligure we went out to Portofino for a few hours but won't go there again. It is filled with luxury shops and high priced restaurants. It is in a very pretty physical setting which is it's best asset.

Given that it's your first trip to Italy and that Portofino is out of the way from your other destinations, I'd say scratch Portofino from your itinerary. Yes, it's pretty, but not significant enough to make it a priority on your first trip. As another poster indicated, it's a place where the mega-rich hang out and shop at high end stores.
You haven't included any information about how many days you are allotting to each stop, nor what your interests are; however, though you didn't ask, I'll add that Pisa is a half day stop. The tower, duomo, and baptistery are what you should see; and they are grouped together. No reason to stay over even one night. Also, how are you planning to travel? Car? More info will help us give you better advice.

I have minimal experience with the area and none with Portofino, though I, too wish to see it as it is home to Castello Brown, filming location of The Enchanted April. I am going to hold off visiting till spring some year.

In case you do decide to visit in October, the Castello Brown seems to be open.

If you decide not to go, consider adding Lucca to the list?

I was there and was disappointed. Luxy shops not much else, it is tiny.
A gd visit in area would be cinque terre. There are 5 villages on the mediterranean. And u can hike betw them then take a boat back to your originating village if the seas are calm. Trains go also from sta maragarita ligure to cinque terre. Imo a great area to visit.

I enjoyed the combination of Portofino, S. Margherita, and Rapallo in late October and did have mostly good weather plus a day of hard rain and wind. There was no swimming, as an earlier storm had already washed a lot of debris down the streams and onto the beaches. Of course, the 5 towns of the Cinque Terre are each equally as picturesque and accessible by train as well as boat. You'll already get a good dose of coastal atmosphere around Positano, earlier in the month.

Florence or Siena would be a more typical choice for a first visit to Italy, with no detour from your route. A Naples-Rome-Florence-Venice route is fast and easy along the central railway line.

Thank you to everyone responding. I'm staying in Naples for three days, Postiano for two, Rome for four days, Pisa half day, Rapallo three days, Venice four days. All on Trenitalia and using public transit.

I think I might do Florence instead. It just seems to make more sense. Portofino sounds like a better trip in the spring or summer as a day trip.

First time in Italy, and you go to Portofino and Pisa, but not to Florence?
Are you kidding me?
Scratch both and go to Florence instead. It's along the high speed rail between Rome and Venice, so it would make perfect sense to stop a couple of days or more there.
End of October is statistically the rainiest time of the year, but who knows? You might get lucky when you go.

It is not the end of the world. Had been in Italy three times before getting to Florence and Rome. And I am still alive.

Have to agree with Roberto, I think you would have a better time scratching Pisa and Portofino/Rapallo and going to Florence for those nights. You can always day trip to Pisa if you really want to and for the coast you are getting that in Positano.
I would also add some time to Positano and remove some from Naples as the tradeoff to give you more coast and less city since you are doing the opposite with the Florence add on.

While I think the Cinque Terre area is great, I think Amalfi Coast is better and the idea of combining the two on one trip never really makes sense to me. See one of them for a little longer and save the other for a 2nd trip to combine with other cities.
A good trip to Italy involves some cities and some coastal or other more natural areas.