OBJECTIVE Thyroid nodules are very common, yet the vast majority are biologically benign. The extreme difficulty facing the clinician selecting potentially malignant thyroid nodules for surgery was the subject of a recent editorial by Ernest L. Mazzaferri in the American Journal of Medicine (93:359-362, 1992). Here we evaluate the potential of proton magnetic resonance spectroscopy (1H MRS) to provide a solution to this problem. METHODS Thyroid tissue from fifty-three patients undergoing partial or total thyroidectomy for solitary thyroid nodules were assessed by 1H MRS. RESULTS When compared with the histologic diagnosis, 1H MRS distinguished normal thyroid tissue (n = 8) from invasive papillary (n = 9), anaplastic (n = 1), and medullary (n = 1) carcinomas with P values of < 0.0001, based on altered cellular chemistry. The same magnetic resonance (MR) criteria categorized pathologically proven follicular carcinoma (n = 8) (established as such by the presence of capsular or vascular invasion at the periphery of the tumor, or by the presence of metastases in the patient) with the other thyroid cancers (P < 0.0001). All other "benign" follicular neoplasms (n = 34), including five atypical follicular adenomas, were assessed by the same 1H MRS criteria and found to fit into one of the two above categories, viz. analogous to benign or malignant thyroid tissue. CONCLUSIONS Proton MRS has the potential to separate out a group of truly benign follicular neoplasms from follicular tumors (both follicular adenomas and follicular carcinomas) that have an atypical follicular pattern on cytologic examination. This is the first report of an objective diagnostic procedure that has the potential to obviate surgical excision in a significant number of patients with benign follicular adenomas, independent of exhaustive histopathologic assessment.