The purpose of this study was to propose and implement a computer aided detection (CADe) tool for breast tomosynthesis. This task was accomplished in two stages-a highly sensitive mass detector followed by a false positive (FP) reduction stage. Breast tomosynthesis data from 100 human subject cases were used, of which 25 subjects had one or more mass lesions and the rest were normal. For stage 1, filter parameters were optimized via a grid search. The CADe identified suspicious locations were reconstructed to yield 3D CADe volumes of interest. The first stage yielded a maximum sensitivity of 93% with 7.7 FPs/breast volume. Unlike traditional CADe algorithms in which the second stage FP reduction is done via feature extraction and analysis, instead information theory principles were used with mutual information as a similarity metric. Three schemes were proposed, all using leave-one-case-out cross validation sampling. The three schemes, A, B, and C, differed in the composition of their knowledge base of regions of interest (ROIs). Scheme A's knowledge base was comprised of all the mass and FP ROIs generated by the first stage of the algorithm. Scheme B had a knowledge base that contained information from mass ROIs and randomly extracted normal ROIs. Scheme C had information from three sources of information-masses, FPs, and normal ROIs. Also, performance was assessed as a function of the composition of the knowledge base in terms of the number of FP or normal ROIs needed by the system to reach optimal performance. The results indicated that the knowledge base needed no more than 20 times as many FPs and 30 times as many normal ROIs as masses to attain maximal performance. The best overall system performance was 85% sensitivity with 2.4 FPs per breast volume for scheme A, 3.6 FPs per breast volume for scheme B, and 3 FPs per breast volume for scheme C.