BACKGROUND: Little is known about the variability of the dermoscopic criteria of squamous cell carcinoma (SCC) according to the histopathological differentiation grade.OBJECTIVES: To evaluate whether specific dermoscopic criteria can predict the diagnosis of poorly differentiated SCC compared with well- and moderately differentiated SCC.METHODS: Clinical and dermoscopic images of SCCs were retrospectively evaluated for the presence of predefined criteria. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot receiver-operator characteristic curves.RESULTS: Of 143 SCCs included, 48 (33·5%) were well differentiated, 45 (31·5%) were moderately differentiated and 50 (35·0%) were poorly differentiated. Flat tumours had a fourfold increased probability of being poorly differentiated. Dermoscopically, the presence of a predominantly red colour posed a 13-fold possibility of poor differentiation, whereas a predominantly white and white-yellow colour decreased the odds of poorly differentiated SCC by 97% each. The presence of vessels in more than 50% of the tumour's surface, a diffuse distribution of vessels and bleeding were significantly associated with poor differentiation, while scale/keratin was a potent predictor of well- or moderately differentiated tumours.CONCLUSIONS: Dermoscopy may be regarded as a reliable preoperative tool to distinguish poorly from well- and moderately differentiated SCC. Given that poor differentiation of SCC represents an independent risk factor for recurrence, metastasis and disease-specific death, identifying poorly differentiated tumours in vivo may enhance their appropriate management.