Renal cell carcinoma (RCC) frequently metastasizes or invades the adrenal gland. Metastatic RCC is often difficult to differentiate from primary adrenal cortical neoplasm (ACN) in an adrenal fine-needle aspiration (FNA). Recently, CD10 immunoreactivity was observed in more than 90% of RCC, but none in primary ACN. To facilitate the accurate diagnosis of metastatic RCC in adrenal FNA, we retrospectively studied the cytomorphology and CD10 immunohistochemistry in 20 cases of FNA specimens, including 10 cases of adrenal FNA (six cases of metastatic RCC and four cases of primary ACN) and 10 cases of primary RCC. Cytomorphologically, several overlapping features were observed between primary ACN and metastatic RCC, including: abundant clear cytoplasm, often with microvesicles, large nuclei with prominent nucleoli, bare nuclei, and prominent vascularity. Immunostaining for CD10 was positive in 9/10 cases of primary RCC, 5/6 cases of metastatic RCC in the adrenal gland, and 0/4 cases of primary ACN. Our study indicates that: 1) an accurate diagnosis of ACN in FNA specimens can often be difficult due to overlapping cytomorphologic features with RCC, and 2) CD10 immunostaining is helpful in separating metastatic RCC from a primary ACN and can reliably be performed on a cytologic sample.