AIDS-Related Lymphoma (ARL) is a disease mediated in part by HIV-infected macrophages and persists despite current HIV therapy protocols. The primary difference between lymphoma seen in non HIV-infected individuals and ARL is that ARL is uniformly high grade and widely metastatic. This fact, coupled with finding almost 50 percent of tumors have HIV expressing macrophages, has created interest in studying a potential viral component to lymphoma evolution. The expansion of HIV quasispecies in vivo, which can be evaluated using a variety of computational algorithms, allows precise assignment of viral evolutionary relationships when applied to sequences obtained from multiple sites of infection. In this study, we used an advanced HIV phylodynamic approach to track the evolution of ARL metastasis in a multisite autopsy study and identified a significant relationship between HIV dynamics and lymphoma progression.