In order to overcome the shortcomings of high false positive rate and poor generalization in the detection of microcalcification clusters regions, this paper proposes a method combining discriminative deep belief networks (DDBNs) to automatically and quickly locate the regions of microcalcification clusters in mammograms. Firstly, the breast region was extracted and enhanced, and the enhanced breast region was segmented to overlapped sub-blocks. Then the sub-block was subjected to wavelet filtering. After that, DDBNs model for breast sub-block feature extraction and classification was constructed, and the pre-trained DDBNs was converted to deep neural networks (DNN) using a softmax classifier, and the network is fine-tuned by back propagation. Finally, the undetected mammogram was inputted to complete the location of suspicious lesions. By experimentally verifying 105 mammograms with microcalcifications from the Digital Database for Screening Mammography (DDSM), the method obtained a true positive rate of 99.45% and a false positive rate of 1.89%, and it only took about 16 s to detect a 2 888 × 4 680 image. The experimental results showed that the algorithm of this paper effectively reduced the false positive rate while ensuring a high positive rate. The detection of calcification clusters was highly consistent with expert marks, which provides a new research idea for the automatic detection of microcalcification clusters area in mammograms.