Rationale:Cases of coexistence of 2 cancers, such as colorectal cancer and diffuse large B-cell lymphoma (DLBCL), colorectal cancer and myelodysplastic syndrome (MDS), and DLBCL with MDS, have been reported, whereas the coexistence of 3 different cancers in a patient is extremely rare. Here we report a case of co-occurrence of colon adenocarcinoma, DLBCL, and MDS in a 78-year-old Chinese man.Patient concerns:He presented to our hospital with palpable lumps in the abdomen without any of the following symptoms including abdominal pain, fever, contact pain, tenesmus, changes in bowel habits and shape, nausea, and vomiting.Diagnoses:The patient was first diagnosed with sigmoid colon adenocarcinoma and DLBCL in the right ascending colon using enhanced computed tomography, colonoscopy, and immunohistochemistry. After resection of the sigmoid adenocarcinoma and DLBCL, MDS was diagnosed according to the results of routine blood tests, bone marrow aspiration smear, and flow cytometry.Interventions:Overall, the patient was treated with surgical resection of the sigmoid adenocarcinoma and DLBCL of the colon, combined with 4 cycles of chemotherapies targeting MDS.Outcomes:Blood test results and follow-up indicated that the treatment regimen showed promising outcomes.Lessons:In conclusion, a case of synchronous existence of colon cancer, DLBCL, and MDS is reported, which suggests that careful attention should be paid clinically to checking the state of bone marrow for elderly cancer patients. Efforts are also needed to establish an effective system for distinguishing the origin of multi-existent cancers and to develop effective therapeutic regimens for multi-existent cancers with fewer side effects.