- Struma ovarii exhibiting malignant histology are uncommon, and an aggressive clinical course in the form of initial extraovarian spread or recurrence is even more exceptional for these tumors. To determine whether specific histologic features have predictive value in distinguishing clinically benign from clinically malignant struma ovarii. Blinded analysis of 19 histologic characteristics of thyroid tumors was performed in 60 clinically benign and 26 clinically malignant struma ovarii cases, with long-term follow-up. Except for lack of fibrosis and macrofollicular pattern, which were more common in biologically malignant tumors (P = .04 and P = .008, respectively), and trabecular pattern, which was associated with a benign clinical course (P = .03), none of the other histologic features was found to be correlated with clinical behavior. The presence of the following features was similar in the biologically benign and malignant tumors: papillae, pseudo-papillae, psammoma bodies, nuclear grooves, nuclear overlap, "orphan Annie" nuclei, nuclear pseudo-inclusions, prominent nucleoli, hypercellularity, colloid scalloping, eosinophilic cytoplasm, mitoses, vascular invasion, cytologic atypia, nuclear pleomorphism, and cell size and type. Trabecular pattern and absence of fibrosis were uncommon, and there was considerable overlap of macrofollicular pattern ratio between benign and malignant cases. Thus, their practical usefulness is uncertain. The clinical outcome of struma ovarii cannot be predicted based on the microscopic diagnosis of the thyroid tissue or on specific histologic features. The lack of correlation between morphology and outcome in proliferative and histologically malignant struma ovarii is striking, making the behavior of these tumors particularly unpredictable.