Background Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma, associated with Merkel cell polyomavirus. MCC admixed with squamous cell carcinoma (SCC) is unassociated with polyomavirus, and is genetically distinct. Objective We sought to distinguish clinically and dermoscopically between MCC and SCC/MCC. Methods We compared patient data for SCC/MCC (n = 26) and MCC (n = 20), and reviewed clinical and dermoscopic images (n = 9) of SCC/MCC. Results Patients with SCC/MCC were older (median 76.5 vs 69 years) and more often male (77% vs 60%), and had more nonmelanoma skin cancer (85% vs 25%), malignant extracutaneous tumors (25% vs 5%), lymphoproliferative disorders (23% vs 10%), and immunodeficient/proinflammatory states (77% vs 35%). In all, 58% of SCC/MCC versus 10% of MCC were clinically diagnosed nonmelanoma skin cancer. Patients with SCC/MCC had more metastases (77% vs 40%), more treatment failures (53% vs 45%), shorter survival (41 vs 54 months), and more death from disease (50% vs 40%). SCC/MCC demonstrated marked scale (7/9), and telangiectasia (1/9). Dermoscopically, small dotted and short linear irregular peripheral vessels and central milky-red areas with large-diameter arborizing vessels were seen. Limitations The rarity of SCC/MCC limits available data. Conclusions SCC/MCC is aggressive, arising within elderly patients’ chronically ultraviolet-exposed skin, often in the setting of immunosuppression or inflammation. Dermoscopically, polymorphous vessels in lesions suspicious for nonmelanoma skin cancer are suggestive.