Before you begin.

1. Backup your current website and database. If you break your site you can easily restore the backup. 
2. Don't upgrade your live website. Either setup a copy on your localhost or buy a month of hosting somewhere. Load a copy of your website, upgrade it and see if anything breaks. If you have any custom coldfusion coding I can guarantee it's going to need a tweek. Fix all the problems on your test site instead of your live website. 
3. Every database query has changed. The request variables for username and password have been changed. This
   <cfquery datasource="#Request.ds#" name="qry_get_products" password="#Request.pass#" username="#Request.user#">
   has become
   <cfquery datasource="#Request.ds#" name="qry_get_products" password="#Request.DSpass#" username="#Request.DSuser#">
   'Request.name' has become 'request.DSname' and 'request.pass' has become 'request.DSpass'. This was done so CFWebstore could work inside other CMS software.
4. In some links the variable #self# has been replaced. This
   #Request.SecureURL##self#?fuseaction...
   has become
   #Request.SecureSelf#?fuseaction...
   Secure links become 'SecureSelf' and unsecure become 'StoreSelf'.

Upgrading to 6.50 from 6.44

1. Replace Files - In the past you could simply replace the few updated files. Since almost every file on the website gets replace you can do it one of two ways.
   1. Use a file comparison software and copy over all the changed files. If you have a lot of custom Coldfusion code this is the recommended way.
   2. Start with a clean copy of 6.50 and modify it to reflect your current layout. Copy your layouts/lay_default.cfm file, css/default.css, and images folder and you're probably good. If you don't have a lot of custom Coldfusion code, this is the way to go.
2. Update database - Run the appropriate sql file (MySQL or MSSQL) in updates/V65update/ with your favorite database editor. 

That's it, not too bad. Good luck.