Jackett LA, Colebatch AJ, Rawson RV, et al. - Given the challenges in the accurate recognition of subtle melanomas and their distinction from benign mimics and that particularly, melanomas bearing resemblance to benign nevi (so-called nevoid melanomas, NMs) and benign mitotically active nevi in pregnancy (MANP) are prone to error. Researchers sought to determine differences in clinical, pathologic, and molecular characteristics between MANP and NMs to aid correct diagnosis and reduce the risk of overtreatment or undertreatment. They evaluated clinicopathologic characteristics of NM (n = 18) and MANP (n = 30) and analyzed mutation data using next-generation sequencing for available cases in each group (NM, n = 8; MANP, n = 12). Innocent histopathologic characteristics apart from increased mitotic activity were noted in all MANP; these were frequently observed in both superficial and deep parts of the lesion (median dermal mitotic rate: 2/mm², range: 1 to 7/mm²). In all cases of NM, they identified a characteristic nevoid silhouette, subtle atypical architectural and cytologic features, and variable mitoses (median mitotic rate: 3/mm², range: 1 to 5/mm²). They identified the median NM tumor thickness of 1.4 mm. Hotspot mutations in NRAS were detected in most NMs (6/8, 75%). NMs vs MANP exhibited noncoding mutations significantly more commonly (median: 4 vs 0). Copy number alterations were uncommon but, when present, were observed in NMs (3/8 NMs vs 0/12 MANP). Alike to conventional common acquired nevi, MANP chiefly harbored driver BRAF mutations, while activating NRAS mutations, noncoding mutations, and copy number alterations were rare. These findings thereby suggest subtle but recognizable distinguishing histopathologic characteristics between NM and MANP that are underpinned by molecular differences. Thus the diagnosis of difficult lesions could be possibly made via a mutation analysis of targeted noncoding mutations.