A 61-year-old female presented with night sweats following a resection for non-Hodgkin's lymphoma of splenium corporis callosi. A positron emission tomography-computed tomography scan demonstrated that original lymphoma activity remained. A new ascending colon mass was identified simultaneously, which was diagnosed as an adenocarcinoma following the surgery. To the best of our knowledge, this is the first case to report a coexistence of primary central nervous system non-Hodgkin's lymphoma and colorectal adenocarcinoma. The case poses a difficult clinical challenge.