Digital breast tomosynthesis (DBT) is under consideration to replace or to be used in combination with 2D-mammography in breast screening. The aim of this study was the comparison of the detection of microcalcification clusters by human observers in simulated breast images using 2D-mammography, narrow angle (15°/15 projections) and wide angle (50°/25 projections) DBT. The effects of the cluster height in the breast and the dose to the breast on calcification detection were also tested. Simulated images of 6 cm thick compressed breasts were produced with and without microcalcification clusters inserted, using a set of image modelling tools for 2D-mammography and DBT. Image processing and reconstruction were performed using commercial software. A series of 4-alternative forced choice (4AFC) experiments was conducted for signal detection with the microcalcification clusters as targets. Threshold detectable calcification diameter was found for each imaging modality with standard dose: 2D-mammography: 2D-mammography (165 ± 9 µm), narrow angle DBT (211 ± 11 µm) and wide angle DBT (257 ± 14 µm). Statistically significant differences were found when using different doses, but different geometries had a greater effect. No differences were found between the threshold detectable calcification diameters at different heights in the breast. Calcification clusters may have a lower detectability using DBT than 2D imaging.