BACKGROUND: Colonic signet-ring cell carcinoma (SRCC) is a rare pathological subtype of colonic tumors. This study aims to comprehensively analyze the clinicopathological characteristics and long-term prognosis of colonic SRCC from multiple perspectives. METHODS: Patients diagnosed with colonic SRCC and mucinous adenocarcinoma (MA) between 2000 and 2021 were retrieved from the surveillance, epidemiology, and end results database. Clinicopathological characteristics were compared using Chi-square tests. Overall survival (OS) and cancer-specific survival (CSS) were assessed using Kaplan-Meier curves and Cox regression analysis. RESULTS: A total of 29,495 patients were enrolled, including 4000 with SRCC and 25,495 with MA. Compared to MA patients, the SRCC cohort was younger, had more males, less differentiation, and higher risks of lymph node (51.2%) and distant (36.6%) metastases. Age, T stage, and M stage were identified as risk factors for lymph node metastasis in SRCC, while age, T stage, and N stage were associated with distant metastasis. SRCC patients demonstrated significantly poorer OS and CSS compared to MA patients (P <
0.001). The 1-, 3-, 5-, and 10-year OS rates for SRCC patients were 57.8, 33.3, 26.0, and 17.1%, respectively, with corresponding CSS rates of 62.8, 39.7, 34.3, and 29.3%. Multivariate Cox regression analysis revealed that age, gender, grade, TNM stage, surgical intervention, chemotherapy, and marital status were predictive of OS, while age, gender, TNM stage, surgery, and marital status were significantly associated with CSS. Notably, female SRCC patients were younger and had a lower incidence of distant metastasis compared to males. Additionally, elderly patients had a higher proportion of females and Caucasians, and a lower incidence of lymph node and distant metastases compared to non-elderly patients. CONCLUSION: Compared to colonic MA, SRCC demonstrates unique clinicopathological features and inferior prognosis, with variations observed across age and gender. Hence, individualized treatment strategies are essential.