I have trouble finding real leather purses, especially good name brands, at thrift stores. Usually some savvy thrift store employ snaps them up, slaps on a hefty price tag, and then puts them behind glass (that is if they even make it to the sales floor in the first place). One thing I have had some luck with are small leather purses. Sometimes these manage to slip by and end up with all the regular purses.
One thing I always recommend when buying secondhand is to try to buy quality items. There's nothing wrong with having a few synthetic purses, but these can easily be purchased new at mass retailers, so for secondhand bags, I try to stick to leather. They are only going to look better with age.
One of the best manufacturers of quality leather goods is Coach. You may think that it is impossible to find Coach secondhand, but I'm speaking from experience, it can be done.
The purses pictured above are secondhand. All are Coach except for the black one in the lower right, it's Etienne Aigner. Coach is perhaps the more desirable brand, but I find this particular Etienne Aigner is on par with Coach as far as style and quality.
The top two purses are from family members, the cream one from my mom and the caramel one from her cousin. They both came from their aunt (my great aunt) and then eventually made their way to me. We usually think of "secondhand" as thrifting, but family members can be a great resource. Be sure to check out the back of your mom's closet and grandma's attic.
The purse on the bottom left is similar to the "Basic Bag" which retails on the Coach site for $168. It was purchased from a now defunct thrift store that benefited a local health clinic for $3.00. They either didn't realize it was Coach or didn't care. Such low pricing could account for why they are no longer in business.
The middle bag is similar to the "Willis Bag" which retails for $298. It was purchased from another local thrift store for $15.00, marked down from a higher price. It was priced a little high for a thrift store bag, but it is definitely a bargain compared to new or even similar used bags on Etsy or Ebay.
The last bag is Etienne Aigner. It is also from a local thrift store, $7.00. Don't automatically dismiss a bag that you don't consider "designer". For thrift store prices, you can usually take a chance on a lesser known brand, all long as the quality is still there.
In my experience, you are going to have a better chance of finding a well priced leather bag at a locally owned thrift store versus one of the larger chains. Be sure to dig through all the racks. You should be able to tell the leather bags from the synthetics based on touch. Look for a style you like, leather that feels good to the touch, high quality stitching, and unusual details like buckles and claps. Finally, remember that the best bag is one that you will actually carry.