Background: Evaluation of patients with cutaneous or subcutaneous nodules, especially if they are multiple, is a diagnostic challenge. This study aimed to investigate smears and cell blocks and compare them with examination of tissue biopsies. Methods: Fine needle aspiration cytology (FNAC) and cell blocks were done for 225 cutaneous and subcutaneous nodules. Furthermore, histopathological examination was conducted using biopsies. Results: According to tissue biopsy, benign lesions constituted the most common finding in 180 (80%) cases. The detected cases were lipoma in 35 (15.5%) cases, adipose tissues in 30 (13.3%) cases, 20 fibro lipomas (8.8%), 20 fibromas (8.8%), 5 juvenile fibroma (2.2%), neurofibroma in 5 cases (2.2%), sebaceous cyst in 25 cases (11.1%), implantation cyst, or dermoid cyst 20 cases (8.8%), pilomatrixoma 5 cases (2.2%), seborrheic keratosis10 cases (4.4%) and Madura foot (actinomycosis) in 5 cases (2.2%). Intermediate lesions of atypical lipoma were found in 20 cases (8.8%). Malignant lesions were 25 cases (11.11%) as follows: 10 cases (4.4%) basal cell carcinoma, 10 cases (4.4%) squamous cell carcinoma and 5 cases (2.2%) basosquamous cell carcinoma. For FNAC smear examination, the sensitivity test was 83.01% and the specificity was 16.66%. For cell blocks examination, the sensitivity and specificity tests were 97.77%, and 100%, respectively. Conclusion: Smear cytology is an easy and quick test for diagnosing skin nodules. Performance of cell blocks improves sensitivity and specificity of smear outcome, but both should be attempted, because the smear may be ineffective in some cases while a cell block cannot be performed in others