The cancer Biomedical Informatics Grid (caBIG) is revolutionizing the way medical researchers share information and collaborate. A key to caBIG's continued success will be interoperability. However, to date, only a single code base (in Java) has been used to create a set of tools and run-time services for caBIG. This paper presents the first significant exploration into the use of Microsoft's .NET Framework and Visual Studio for caBIG. Given its substantial existing community, a .NET-based set of tools for caBIG can significantly increase the pool of qualified software designers and developers for caBIG. Arguably more importantly, a second development foundation could facilitate revisiting a broad set of design decisions made to date in caBIG that have perhaps been unduly based directly or indirectly on a single underlying software technology. We begin by describing issues we have encountered in building relatively simple .NET-based clients to existing caBIG services. Next, ...