Klb_Arc,  It will be based on whether the existing 4GB dimms are Udimms or Rdimms. If the 4GB dimms are UDimms then the only option you would have would be adding more of the 4GB dimms to reach 48GB. Now if they are Rdimms you more options. With Rdimms you can go to 96GB with 12 8GB dimms, or even 192GB, if you were to chose 12 16GB dimms. With mixing them I would suggest adding 4 8GB dimms and placing them in A1, A2, B1, and B2. Then place the 4 4GB dimms in slots A4, A5, B4, and B5. That would leave you with a total of 48GB total. Now you can add and remove some of the dimms for different configurations, this is just a suggestion.  Let me know if this helps answer your questions. 
Looking to possibly upgrade the RAM on an R420: dual processor (2 x Intel Xeon E5-2430 2.2GHz), Server 2012 64bit. It currently has 16GB RAM (4 x 4GB @ 1333 MHz); system info reports 12 total slots. What are the possible configuration/ranking options with adding additional 4GB and/or 8GB sticks? I don't necessarily have a desired GB level to reach, but I'd at least like to get to 24GB. (I saw a couple similar posts, but not with my exact configuration, so hopefully this is not considered a duplicate)      
R420 RAM upgrade