The participation of a specific subset of B cells and how they are regulated in cancer is unclear. Here, we demonstrate that the proportion of CD5⁺ relative to interleukin-6 receptor α (IL-6Rα)-expressing B cells was greatly increased in tumors. CD5⁺ B cells responded to IL-6 in the absence of IL-6Rα. IL-6 directly bound to CD5, leading to activation of the transcription factor STAT3 via gp130 and its downstream kinase JAK2. STAT3 upregulated CD5 expression, thereby forming a feed-forward loop in the B cells. In mouse tumor models, CD5⁺ but not CD5^– B cells promoted tumor growth. CD5⁺ B cells also showed activation of STAT3 in multiple types of human tumor tissues. Thus, our findings demonstrate a critical role of CD5⁺ B cells in promoting cancer.