In the present study we evaluated comparatively the diagnostic value of mammography, of 99mTc-sestamibi scintimammography (sestamibi-SC) and of colour Doppler ultrasonography (CD-US) in 116 breast lesions. Diagnosis was based on histopathological examination. Overall, out of 86 malignant tumours, 80 (93%) and 75 (87%) had a positive sestamibi-SC and positive CD-US, respectively. Out of 30 benign lesions, 25 (83%) and 26 (87%) had a negative sestamibi-SC and negative CD-US respectively. The true positive results were similar in palpable and in non-palpable lesions for both methods. Out of 19 non-palpable malignant tumours, mammography confirmed malignancy in only one case (5%), which was significantly lower than the results obtained by sestamibi-SC (89%; Px0.0001) and by CD-US (74%; P=0.0001). In palpable malignant tumours, by using mamography, true positive results were obtained in 54/67 (80.5%) patients, which was significantly lower than the results obtained by sestamibi-SC (94%; P=0.03) and marginally different to the results obtained by CD-US (91%; P=0.13). It is concluded that sestamibi-SC and CD-US are useful tools in clarifying the nature of breast lesions in cases with doubtful mammography. The clinical value of these diagnostic procedures in guiding subsequent therapeutic interventions requires further investigation.