Co-occurrence of two types of cancers, especially lung and colorectal cancers is rare. This study investigated patients at Bach Mai Hospital who were diagnosed with two or three cancers. Only a few patients concurrently had two cancers. Positron emission tomography (PET)/computed tomography (CT) was used for the staging of cancer, especially synchronous malignancies. In this report, we have presented the case of a patient diagnosed with rectal and lung cancer based on CT, magnetic resonance imaging, and PET/CT scans as well as immunohistochemistry. Managing terminal synchronous cancers is challenging. The efficacy of the preferred anticancer therapy must be considered to ensure patients’ quality of life. Although the combination of tyrosine kinase inhibitor-targeted therapy and chemotherapy is promising, its toxicity remains unknown. Our patient received two cycles of mFOLFOX6, afatinib, and bisphosphonate. However, the treatment was discontinued due to grade 3 stomatitis and grade 2 anemia. Despite recovery and partial response in terms of symptom and tumor marker reduction, the patient refused further treatment and chose palliative care.