The clinical significances of de novo and nevus-associated melanomas are controversial. In this study, we investigated the correlations of these forms of melanomas in respect to their pathological and clinical features and patient outcomes. The data of 660 pathologically confirmed Turkish-Caucasian melanoma patients, whose tumors were either associated with a pre-existing melanocytic nevus or not, were analyzed retrospectively. They were treated and followed up at a single tertiary referral center. A total of 440 de novo (66.7%) and 220 nevus-associated melanomas (33.3%) were enrolled into the study. The median age of the patients was 51 years. The patients consisted of 341 men (51.7%) and 319 women (48.3%). There were significant correlations between de novo melanomas and advanced age (p = 0.003), tumor thickness greater than 2 mm (p = 0.0001), ulceration (p = 0.01) and high mitotic rate (p = 0.03). On the other hand, nevus-associated melanomas were found significantly associated with histological regression (p = 0.03) and BRAFV600E mutation (p = 0.003). Most of the nevus-associated melanomas were found on trunk and head/neck, whereas extremities were more frequently inflicted by de novo melanomas (p = 0.0001). Furthermore, none of other variables, such as sex, histopathology, lymph node involvement and presence of metastasis, showed statistically significant difference between de novo and nevus-associated melanoma patients (p > 0.05). The 5-year DFS rates were 62.4% and 72.7% for de novo melanoma and for nevus-associated melanoma patients, respectively (p = 0.1). The 5-year OS rate were 72.1% and 76.4% for de novo melanoma and nevus-associated melanoma patients, respectively (p = 0.2). In conclusion, even though de novo melanomas are more significantly correlated with aggressive histopathologic variables, such as tumor depth, ulceration and high mitotic rate, the survival rates of de novo and nevus-associated melanomas are similar.