Abstract Background The etiology of idiopathic guttate hypomelanosis (IGH) remains uncertain; however, solar exposure and heredity have been proposed as causative factors. Objective To explore the genetic predisposition to the development of IGH. Methods A comparative case–control study was performed at a dermatology department at a university hospital. Forty‐seven subjects (22 renal transplant patients and 25 controls) were enrolled. Clinical examination and human leukocyte antigen (HLA) determination were performed. Results In the group of subjects with HLA‐DQ3 (10/13, P = 0.025), there was a statistically significant ( P < 0.05) positive association for the presence of IGH; in the group of subjects with HLA‐DR8 (6/6, P = 0.023), there was a statistically significant negative association for the presence of IGH. Conclusions The presence of HLA‐DQ3 in patients with IGH suggests a genetic basis in a group of renal transplant subjects. HLA‐DR8 was found in patients without IGH, and it could play a role as a “protective factor” preventing subjects from developing IGH.