Synchronous squamous cell carcinoma of the head and neck (HNSCC) and non-Hodgkin's lymphoma is a rare clinical scenario. It is unknown whether the R-CHOP chemotherapy for lymphoma would also be active against HNSCC. Herein, we present such a case and a review of the literature. A 64 year-old female presented with painless jaundice. CT demonstrated a retroperitoneal mass and pathology showed follicular lymphoma. A base-of-tongue HPV squamous cell carcinoma was found incidentally on staging CT. R-CHOP chemotherapy was initiated. After 3 cycles of R-CHOP the lymphoma had a complete metabolic response and, unexpectedly, the HNSCC also demonstrated excellent response. The patient received another 3 cycles followed by radiation to the HNSCC and to date is in remission for both cancers. This case highlights the exquisite sensitivity of HPV-related HNSCC, which should be taken into consideration in treatment prioritization of a concurrent diagnosis of a second cancer.