Objective To investigate the clinical features, histopathological features and diagnosis of seborrheic keratosis (SK). Methods A total of 242 SK patients admitted to the Department of Dermatology, Shanghai Jiading District Hospital of Traditional Chinese Medicine from January 2018 to January 2023 were selected as the research objects, and the relationship between different clinical manifestations of skin lesions and histopathological characteristics was analyzed. Results The ratio of male to female SK was 5∶7. There was no significant difference in histopathological types between different genders (P >0.05). The age of onset of SK was 25-88 years old, and the peak age of onset was 31-70 years old. The incidence of high age group was higher than that of low age group (P <0.05). There was no significant difference in histopathological types between different sites (P >0.05). The diameter of SK lesions was 0.2-2.6 cm, and the lesions with diameter of 0.5-1 cm, medium quality, clear boundary, typical shape and graywhite color accounted for a higher proportion. The pathological types of 242 patients were hyperkeratosis in 46 cases (19.01%), acanthosis in 87 cases (35.95%), adenoid in 34 cases (14.05%), flat in 27 cases (11.16%), clonal in 9 cases (3.72%), stimulating in 22 cases (9.09%), melanoma in 4 cases (1.65%) and mixed in 13 cases (5.37%). According to the clinical manifestations, 116 cases (47.93%) were diagnosed as SK, and 73 cases (30.17%) were misdiagnosed as pigmented nevus. Conclusion The clinical histopathological examination of SK is helpful to confirm the diagnosis and reduce misdiagnosis.