Malignant melanoma, a highly malignant tumor predominantly found on the skin surface, has exhibited an alarming rise in both incidence and mortality rates annually since 2012. Despite its relatively low occurrence among skin malignancies, the mortality rate of malignant melanoma remains disproportionately high. The prognosis relies heavily on early stage detection, with a significant disparity in survival rates between stage I and stage IV patients. Studies exploring insulin resistance (IR) as a potential risk factor for malignant melanoma are scarce. The present study therefore investigated the association between the triglyceride glucose (TyG) index, an indicator of IR, and malignant melanoma incidence. Retrospective data from patients diagnosed with malignant melanoma at the First Affiliated Hospital of Nanjing Medical University (Nanjing, China) between January 2019 and January 2024 were collected. Basic information, including age, sex and body mass index, and hematological test results, such as those for fasting triglycerides and fasting blood glucose, were analyzed. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were employed to explore the association between melanoma risk and the TyG index. A total of 403 participants, including 272 patients with malignant melanomas and 131 patients with nevi, were included in the study. The melanoma group exhibited significantly higher levels of the TyG index compared with the control group (P<
0.001). Univariate and multivariable logistic regression analyses revealed the TyG index as an independent risk factor for melanoma incidence (OR, 6.33
95% CI, 3.56-11.27
P<
0.001). Incidence rates of melanoma significantly increased across tertiles of the TyG index (P<
0.001). The ROC curve analysis identified a clinically acceptable predictive cutoff point for the TyG index. The present study therefore provides evidence that the TyG index is a significant risk factor for the incidence of malignant melanoma. The findings underscore the potential utility of the TyG index as a biomarker for diagnosing melanoma and suggest new avenues for melanoma treatment strategies.