Adrenal cortical epithelial tumours are common in ferrets. A variant tumour type with prominent spindle cell proliferation has been identified. We characterized these variant tumours with light microscopy and immunohistochemical analysis and correlate these features to clinical parameters and prognosis. We classified 24 ferret adrenal cortical masses with recognizable spindle cell proliferation obtained from the AMC and AFIP databases, based on percentage of spindle cells present and features of malignancy. These masses were separated into hyperplastic nodules and adenomas (both with 1-24% spindle cells), 'mixed' adenomas (>or=25% spindle cells), adenocarcinomas (1-24%) and 'mixed' adenocarcinomas (>or=25% spindle cells). Tumours were evaluated immunohistochemically for smooth muscle actin (SMA) and estrogen receptor (ER) expression. Disease-free interval (DFI) and survival time (ST) were calculated using Kaplan-Meier product limit method. Of 24 cases of spindle cell variant adrenal tumours, one was a hyperplastic nodule, 10 were adenomas, three were 'mixed' adenomas, six were adenocarcinomas and four were 'mixed' adenocarcinomas. The proliferative spindle cell cytoplasm was SMA-positive (smooth muscle myocyte origin). ER positivity, seen in nine of 24 cases, was restricted to adenocarcinomas, 'mixed' adenomas and 'mixed' adenocarcinomas. DFI and ST were significantly reduced in 'mixed' adenocarcinomas or tumours with ER expression. DFI was significantly reduced in tumours with marked smooth muscle. The spindle cell component of these variant adrenal tumours is smooth muscle in origin. The presence of abundant smooth muscle, a more malignant histologic grade ('mixed' adenocarcinomas) and ER expression are significantly positively correlated to both decreased DFI and decreased ST.