The histopathologic features of 10 myxoid adrenocortical neoplasms were analyzed, and epidermal growth factor receptor (EGFR) expression, EGFR gene copy number, and EGFR gene mutations in the 10 tumors were detected by using immunohistochemical analysis, fluorescence in situ hybridization, and the Scorpion Amplification Refractory Mutation System (DxS, Manchester, England), respectively. Histologically, all 10 tumors varied in their myxoid composition, ranging from 20% to 95%. EGFR protein overexpression was more frequent in myxoid adrenocortical carcinomas (3/4) than in myxoid adrenocortical adenomas (0/6). However, EGFR mutations and EGFR amplification were rare. All patients with adenomas survived for the follow-up period with no recurrence of their tumors or evidence of metastatic disease; 3 patients with carcinoma died of the disease, and 1 is alive with disease. Myxoid changes in adrenocortical neoplasms can be present in adenomas and carcinomas. Detection of EGFR protein expression may be useful in the differential diagnosis between adrenocortical adenomas and adrenocortical carcinomas.