Disclosed herein are methods of detecting malignancy in a tumor of a subject comprising measuring the amount of 5-hmC in a tumor sample and comparing to a control to thereby detect a level of reduction of 5-hmC in the tumor, wherein the tumor is characterized as malignant if a threshold level of reduction is detected. The tumor may be a solid tumor such as a melanocytic lesion. Also disclosed are methods of determining the prognosis of a subject with a tumor by determination of the amount of 5-hmC in the tumor. Methods for treatment of a tumor with reduced 5-hmC are also disclosed.