The triple assessment in the pre-operative evaluation of breast cancer has been practiced in some hospitals in Tanzania. However, its validity and reliability has not been evaluated in any hospital in the country including the study area. This cross-sectional study was conducted at Bugando Medical Centre in northwestern Tanzania to determine the validity, reliability and applicability of triple assessment as an alternative to conventional open biopsy in the pre-operative diagnosis of breast cancer. A total of 212 female patients aged 35 years and above were studied. All patients underwent clinical evaluation, mammography and fine needle aspiration cytology. Histopathology was done to confirm the diagnosis. One hundred and twenty (56.6 %) patients with a median age of 36 years had benign lesions and the remaining ninety-two (43.4%) with a median age of 47 years had breast cancer (P = 0.002). With triple assessment, 92 patients were diagnostic for malignancy and 120 benign, respectively confirmed by histopathology. The Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value and Accuracy were 100.0%. There were no false positive or false negative results. The Kappa statistic for the combination was 1.0 implying excellent agreement with histopathology. The majority of patients (59.9%) underwent triple assessment on the same day with results being available to the patient within 24 to 72 hours. The triple assessment is an accurate and quick method for the evaluation of breast cancer and can be applied as a safe alternative for open biopsy when it is concordant..