Background Spitzoid melanocytic neoplasms are well known to be diagnostically challenging. Immunohistochemistry (IHC) and molecular approaches have been used as ancillary diagnostic tests. Herein, we investigate the use of PRAME IHC for the assessment of spitzoid melanocytic neoplasms. Methods Ten Spitz nevi, 14 atypical Spitz tumors, and 11 spitzoid melanomas were retrieved, and PRAME IHC was scored on a scale of 1–4 (in % quartiles). Intensity of staining was categorized as weak or strong. Cases with no staining received a score of 0. Positive lymph nodes from three spitzoid melanomas were also analyzed. Results Spitz nevi, atypical Spitz tumors, and spitzoid melanomas had mean PRAME IHC scores of 1.20, 0.93, and 3.36, respectively. The percentage of cases with a score 3 or higher for each category of spitzoid neoplasms are as follows: Spitz nevus (20%), atypical Spitz tumor (0%), and spitzoid melanoma (82%). Among the spitzoid melanomas, three cases had positive sentinel lymph nodes, which showed PRAME score of 2, 4, and 4 in the metastatic deposits. Conclusions Previous reports revealed PRAME IHC as useful tool to distinguish benign from malignant melanocytic lesions. The results presented here are concordant with the prior studies, but expand the application of this marker to Spitz nevi/tumors and spitzoid melanomas. The present findings suggest the potential diagnostic utility of PRAME IHC in the assessment of spitzoid melanocytic lesions, particularly in distinguishing spitzoid melanomas from Spitz nevi and atypical Spitz tumors.

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