Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease of the colon and rectum. Its etiology and pathogenesis are incompletely elucidated, although there are many studies concerning these problems. Chronic inflammation and immunosuppressive treatment are risk factors for epithelial and lymphoid malignancies. We present a case of a 39-year-old man who died after a long-standing untreated UC complicated with mantle cell colonic lymphoma and then with transformation towards a high grade diffuse large B cell lymphoma. Multiple colonic biopsies were collected in various moments of the disease. Microscopic and immunohistochemical features are comparatively presented. This case emphasizes the importance of constant surveillance for UC patients and reaffirms the role of multidisciplinary approach in UC management.