The information captured by the gist signal, which refers to radiologists’ first impression arising from an initial global image processing, is poorly understood. We examined whether the gist signal can provide complementary information to data captured by radiologists (experiment 1), or computer algorithms (experiment 2) based on detailed mammogram inspection. In the first experiment, 19 radiologists assessed a case set twice, once based on a half-second image presentation (i.e., gist signal) and once in the usual viewing condition. Their performances in two viewing conditions were compared using repeated measure correlation (rm-corr). The cancer cases (19 cases × 19 readers) exhibited non-significant trend with rm-corr = 0.012 (p = 0.82, CI: −0.09, 0.12). For normal cases (41 cases × 19 readers), a weak correlation of rm-corr = 0.238 (p < 0.001, CI: 0.17, 0.30) was found. In the second experiment, we combined the abnormality score from a state-of-the-art deep learning-based tool (DL) with the radiological gist signal using a support vector machine (SVM). To obtain the gist signal, 53 radiologists assessed images based on half-second image presentation. The SVM performance for each radiologist and an average reader, whose gist responses were the mean abnormality scores given by all 53 readers to each image was assessed using leave-one-out cross-validation. For the average reader, the AUC for gist, DL, and the SVM, were 0.76 (CI: 0.62–0.86), 0.79 (CI: 0.63–0.89), and 0.88 (CI: 0.79–0.94). For all readers with a gist AUC significantly better than chance-level, the SVM outperformed DL. The gist signal provided malignancy evidence with no or weak associations with the information captured by humans in normal radiologic reporting, which involves detailed mammogram inspection. Adding gist signal to a state-of-the-art deep learning-based tool improved its performance for the breast cancer detection.