We herein report a case of colonic polyposis, colorectal carcinoma and large B-cell lymphoma in a 22-year-old male patient with a previous history of childhood lymphoblastic lymphoma. Eight years after lymphoblastic lymphoma, which presented as mediastinal mass and superior vena cava syndrome, the patient complained of abdominal pain, lower gastrointestinal bleeding and an abdominal mass. The surgical exploration revealed numerous mucosal polyps throughout the large intestine, and multifocal masses in the ascending and transverse colon and the rectosigmoid region. A retroperitoneal mass was also found. The pathological examination revealed >100 tubular adenomatous polyps and a multifocal, well-differentiated adenocarcinoma, with lymph node involvement and pericolic invasion. Interestingly, the immunohistochemical studies confirmed the malignant undifferentiated retroperitoneal mass as large B-cell lymphoma. Over a period of ~10 years, the patient had suffered from three different malignancies. To the best of our knowledge, such a combination of sporadic adenomatous colonic polyposis, colorectal carcinoma and two extra-intestinal non-Hodgkin lymphomas has not been reported to date. It should be considered that each malignancy increases the risk for other neoplastic diseases and a close follow-up is crucial for early detection of second malignancies and neoplastic syndromes.