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People miss a large proportion of targets when they only appear rarely. This Low Prevalence (LP) Effect could lead to serious consequences if it occurred in the real-world task of searching for cancers in mammograms. Using a novel mammogram search task, we asked participants to search for a prespecified cancer (Experiments 1–2) or a range of masses (Experiments 3–5) under high or low prevalence conditions. Experiment 1 showed that an LP Effect occurred using these stimuli. Experiment 2 tested an overreliance hypothesis and showed that the use of Computer Aided Detection (CAD) led to fewer missed cancers with a valid CAD prompt yet, a large proportion of cancers were missed when CAD was incorrect. Experiment 3–5 showed that false alarms also increased when searching for a range of masses and that CAD reduced miss errors when it correctly cued the target but increased miss errors and false alarms when it did not. Furthermore, when a mass fell outside the CAD prompt it was more likely to be misidentified. No LP Effect was observed with the addition of CAD when people were asked to search for a range of targets. Theories and implications for mammogram search are discussed.