Synchronous diagnosis of acute myeloid leukemia (AML) and symptomatic multiple myeloma (MM) is a rare situation that poses serious therapeutic difficulties. We report the case of a 68-year-old male which evolved simultaneously to symptomatic MM and AML. Both diseases first responded to treatment for 40 months after 7+3 induction and maintenance therapy of azacytidine + lenalidomide. MM relapsed first and was treated with azacytidine + daratumumab, which led an additional 15 months of progression-free survival. Little myeloid clonal size reduction over time was seen. This case shows that AML and MM can be effectively treated simultaneously using appropriate combinations.