BACKGROUND: The incidence of malignant gastrointestinal (GI) tumors is increasing, and advancements in medical care have significantly improved patient survival rates. As a result, the number of cases involving multiple primary cancers (MPC) has also increased. The rarity of MPC and the absence of sensitive and specific diagnostic markers often lead to missed or incorrect diagnoses. It is, therefore, of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease. Patients with GI malignancies face a higher relative risk of developing additional primary malignant tumors compared to those with other systemic tumors. Vigilant monitoring and follow-up are crucial, especially for high-risk groups, which include older adults, men, those with addictions to alcohol and tobacco, those with a family history of tumors, and those who have undergone radiotherapy. CASE SUMMARY: In this article, we report three cases of MPC, each involving malignant tumors of the GI tract as the initial primary carcinoma, offering insights that may aid in effectively managing similar cases. CONCLUSION: Patients with GI malignancies face a higher MPC risk. Developing screening and follow-up protocols may enhance detection and treatment outcomes.