Purpose: To determine the feasibility of T1-201 as a tumor localizing agent in palpable and nonpalpable breast lesions, in comparison with mammography and ultrasonography (US), and to evaluate the contribution of these modalities to each other in obviating biopsy. Materials and Methods: Seventy-two palpable and nonpalpable breast lesions were prospectively classified as benign, indeterminate, or malignant according to the sonographic and mammographic criteria and were further analized with T1-201 scanning. These classifications were compared with biopsy results. The sensitivity, specificity, accuracy, false positive and false negative rates (FPR, FNR), negative and positive predictive values (npv, ppv) were calculated for each individual modality and combination of modalities to evaluate the contribution of these three techniques to each other. Results: Of 72 lesions 52 were histologically malignant and 20 were benign. Overall, mammography was the most sensitive (92%) and T1-201 was the most specific (75%) of the three modalities. Mammography + T1 combination was the most specific (90%) and accurate (97%) of dual combinations. In mammographically or sonographically indeterminate cases, T1-201 was much more specific (75% versus 37% for mammography and US) and more accurate (82% versus 36% for mammography and 54% for US) than the other two modalities, and mammography + T1 combination was significantly superior to other dual combinations (87% specific and 91% accurate). Use of T1-201 scanning as an adjunct to mammography + US combination increased the specificity, ppv, and accuracy rates overall, particularly in mammographically or sonographically indeterminate cases. Conclusions: In mammographically and sonographically indeterminate breast lesions thallium scanning may be offered as a third step of investigation to obviate biopsy. (C) 1997 Elsevier Science Ireland Ltd.