Insulin resistance and obesity are suggested to have a key role in the molecular pathogenesis of various disorders, including several malignancies. Moreover, insulin resistance has recently been found to be associated with cutaneous and uveal melanoma, while a variable positive correlation between obesity and the risk of cutaneous melanoma was also found at least in men. The present trial aims at confirming whether insulin resistance, assessed with the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI), is a risk factor for cutaneous melanoma. One hundred and thirty patients diagnosed with cutaneous melanoma and 130 age-, sex-, and skin phototype-matched controls were evaluated. At the univariate and multivariate analysis, the diagnosis of cutaneous melanoma was inversely related with insulin resistance (HOMA-IR) and positively with BMI (p = 0.0014 and p = 0.008, respectively). Consistently, insulin sensitivity (QUICKI) and BMI resulted positively associated with the diagnosis of cutaneous melanoma (p = 0.0001 and p = 0.0026, respectively). The results obtained are partially in agreement with those reported in the literature. By comparing our data with those generated by other studies, inconsistencies in key features among subgroups of different trials have emerged, possibly affecting final correlations. Based on insulin resistance/sensitivity, fasting insulinemia/glycemia, and BMI values collected from patients who participated in the present trial, two nomograms potentially assessing the risk of cutaneous melanoma have been generated. Molecular aspects sustain a role for insulin resistance in the carcinogenesis of cutaneous melanoma, but clinical data remain uncertain. Larger, well-balanced, correlative trials are still needed to define the potential role of insulin resistance in the carcinogenesis of cutaneous melanoma.