Yes, you can run Amazon's Kindle for PC off of a USB thumb drive. The application can be installed from the Kindle website onto the USB thumb drive. You will be able to access and use the application from any computer that has the necessary system requirements, without needing to install the application onto each computer. However, you will need to set up the preferences of the application and make any necessary changes to the bookmarks, notes, and highlights within the application for each computer you use. Additionally, once the application is used on any computer, the USB thumb drive must remain connected to the device even when not using the application.