Purpose of Review <p>Squamoid eccrine ductal carcinoma (SEDC) is a rare and aggressive skin cancer originating from eccrine glands, often misdiagnosed as squamous cell carcinoma (SCC). This review aims to synthesize existing data on SEDC epidemiology, pathophysiology, clinical manifestations, diagnosis, histopathology, immunohistochemistry, treatment approaches, prognosis, and follow-up.</p> Recent Findings <p>A systematic literature search identified 92 cases of SEDC with a mean patient age of 69. Clinically, SEDC presents as a single dermal nodule, ranging from benign appearing to rapidly growing, locally destructive plaques. Sun-exposed areas, particularly the head and neck, accounted for 73% of all reported cases. Histopathological analysis reveals superficial components mimicking well-differentiated SCC, with deeper portions exhibiting eccrine ductal differentiation and infiltrative growth. Immunohistochemical markers such as CK5/6, p63, EMA, and CEA are consistently positive, with CK7 and BerEP4 showing mixed expressions. Treatment primarily consists of wide local excision (65.2%) and Mohs micrographic surgery (MMS) (27.1%), with MMS demonstrating lower recurrence rates in some studies. Adjuvant therapies, including radiotherapy and hormonal therapy, are employed in metastatic cases.</p> Summary <p>SEDC is characterized by a high recurrence rate of 17% and poor post-surgical 5-year survival rates of less than 30%. Given the rarity of this carcinoma, treatment recommendations are largely based on case reports and small series. Early diagnosis, aggressive management, and close follow-up are essential to optimize outcomes in patients with SEDC.</p>