To evaluate the frequency of missed cancers on breast MRI in women participating in a high-risk screening program. Patient files from women who participated in an increased risk mammography and MRI screening program (2003-2014) were coupled to the Dutch National Cancer Registry. For each cancer detected, we determined whether an MRI scan was available (0-24 months before cancer detection), which was reported to be negative. These negative MRI scans were in consensus re-evaluated by two dedicated breast radiologists, with knowledge of the cancer location. Cancers were scored as invisible, minimal sign, or visible. Additionally, BI-RADS scores, background parenchymal enhancement, and image quality (IQ; perfect, sufficient, bad) were determined. Results were stratified by detection mode (mammography, MRI, interval cancers, or cancers in prophylactic mastectomies) and patient characteristics (presence of BRCA mutation, age, menopausal state). Negative prior MRI scans were available for 131 breast cancers. Overall 31% of cancers were visible at the initially negative MRI scan and 34% of cancers showed a minimal sign. The presence of a BRCA mutation strongly reduced the likelihood of visible findings in the last negative MRI (19 vs. 46%, P < 0.001). Less than perfect IQ increased the likelihood of visible findings and minimal signs in the negative MRI (P = 0.021). This study shows that almost one-third of cancers detected in a high-risk screening program are already visible at the last negative MRI scan, and even more in women without BRCA mutations. Regular auditing and double reading for breast MRI screening is warranted.