Background: Multiple studies have described associations between infiltrating immune cells, prognosis and treatment response in cancer. However, the clinical relevance has most often been attributed to the T-cell linage, whereas the humoral immune response is less investigated. In colorectal cancer (CRC), accumulation of CD20-positive B lymphocytes at the advancing margin of metastatic CRC has been demonstrated to correlate with prolonged survival. This study aimed to further investigate the clinicopathological correlates and prognostic impact of B cell and plasma cell infiltration in colorectal cancer (CRC). Methods: Immunohistochemical expression of CD20 and CD138 in was analyzed in tissue microarrays with tumors from 557 incident cases of CRC from the Malmö Diet and Cancer Study, a prospective population-based cohort. Kaplan-Meier analysis and Cox regression analysis were used to determine the impact of CD20 and CD138 expression on 5-year overall survival (OS). Results: CD20 expression could be evaluated in 549 (98.6 %) cases and CD38 in 534 (95.9 %) cases. CD20 expression correlated significantly with both immune cell-specific and tumor-specific expression of CD138 (p < 0.001 and p = 0.001, respectively). Furthermore, immune cell-specific CD20 and CD138 expression as well as tumor-specific CD138 expression correlated significantly with lower T-stage (p < 0.001, p < 0.001 and p = 0.002, respectively). A higher density of CD20+ cells correlated significantly with an improved OS (HR = 0.66, 95 % CI 0.50-0.86), remaining significant in multivariable analysis adjusted for age, TNM stage, differentiation grade and vascular invasion (HR = 0.65; 95% CI 0.48-0.90). Neither immune cell nor tumor cell-specific CD138 expression was significantly associated with prognosis. Conclusions: Our results demonstrate that increased B cell infiltration in CRC is an independent factor of improved prognosis. Moreover, the study provides a first demonstration of the expression and clinicopathological correlates of immune cell-specific CD138 expression in CRC, thus providing a further characterization of the immune landscape in this type of cancer.