BACKGROUND AND OBJECTIVES: Dermatofibromas (DFs) are common benign skin lesions with unclear etiology, possibly reactive or tumoral. This study aims to evaluate the incidence of DF misdiagnosis and to correlate histopathological findings with clinical interpretations. METHODS: The extraction for this retrospective study was conducted from 8035 excisions performed between 2016 and 2022 by 9 physicians. A total of 50 cases with conclusive histopathological diagnoses of DF and 33 clinical cases of DF were identified. A p value of <
0.05 was considered statistically significant. RESULTS: The clinical arm included 33 cases, with 7 having DF in the differential diagnosis. The mean age for a confident DF diagnosis was 57.86 years, compared to 44.35 years for a probable diagnosis (p = 0.023). Diagnosis accuracy was 69% for certain cases versus 43% for probable cases. DF on legs had higher clinical uncertainty, 6/7 versus 9/26 (p = 0.016). In the histopathological arm of 50 patients, lesions on lower extremities had higher correct diagnosis rates (p = 0.024) and were least accurate on the torso (p = 0.009). CONCLUSIONS: DF can pose a challenge even for experienced clinicians. Location is crucial as DF may escape diagnosis in less common areas. Patients' age and physician's expertise induce uncertainty.