MicroRNA-106b (miR-106b) is overexpressed in various types of cancers and is associated with the regulation of carcinogenic processes. However, its clinical significance in cutaneous melanoma has not been reported. qRT-PCR was performed to examine the expression of miR-106b in 15 cases of dysplastic nevi, 17 cases of melanoma metastases, and 97 cases of primary cutaneous melanoma tissue samples. Survival rate was determined with Kaplan-Meier and statistically analyzed with the log-rank method between groups. Survival data were evaluated through multivariate Cox regression analysis. Significant differences in miR-106b expression were shown between dysplastic nevi and primary cutaneous melanomas (P < 0.01), between primary melanomas and metastatic cutaneous melanomas (P < 0.01), and between primary cutaneous melanomas and metastatic cutaneous melanomas (P < 0.001). We found that high miR-106b expression was correlated with Breslow thickness (P = 0.002), tumor ulceration (P = 0.002), and advanced clinical stage (P < 0.001). The patients with high miR-106b expression showed shorter 5-year overall survival than those with low miR-106b expression (P = 0.02; log-rank test). Multivariate regression analysis showed that the status of miR-106b expression was an independent prognostic factor for overall survival (HR = 2.09, 95%CI: 1.11-10.26, P = 0.02). This study showed that miR-106b may contribute to the progression of cutaneous melanoma and its up-regulation may be independently associated with poor prognosis of cutaneous melanoma. This suggests that miR-106b might serve as a promising biological marker for further risk stratification in the management of cutaneous melanoma.