Currently, the occurrence of multiple primary malignant tumors is one of the complex and poorly understood issues of oncology. After the diagnosis of malignant neoplasm is established, the risk of a new primary, non-metastatic tumor increases in a patient. The paper presents a case report of the patient with four multiple primary malignant tumors in the duodenum and colon. Synchronous cancer of the cecum and rectosigmoid junction occurred after 9 months of the duodenal cancer pancreatoduodenal resection, photodynamic therapy, and 12 multiagent chemotherapy courses. The patient received 8 courses of chemotherapy with capecitabine, during which cancer progression was reported, and 16 multiagent chemotherapy courses. Two years later rectal cancer occurred, due to which rectal re-resection was conducted, along with 4 multiagent chemotherapy courses and target therapy. This clinical case emphasizes that it is necessary to perform additional assessment when treating patients with synchronous or metachronous multiple primary tumors to ensure the timely diagnosis and multidisciplinary approach to treatment of cancer patients.