False-negative screening mammograms generally refer to breast cancers that were overlooked or misinterpreted at screening. An important question is whether earlier detection could have made a difference in the prognosis of the women concerned. We reviewed screening and diagnostic mammograms of 234 screen-detected and interval cancer cases (aged 44-84 years) diagnosed between 1991 and 1996 in the Nijmegen breast cancer screening programme. A lesion was visible on 117 (50%) of the screening mammograms prior to the diagnosis of breast cancer. Fifty-one out of the 117 cancers had poor prognostic characteristics at diagnosis (i.e. N+ and/or T2+) and could potentially have benefited from an earlier diagnosis ('possible gain'). The 'possible gain' cases were more often characterised by architectural distortion (29 vs. 10%; P=0.01) or a high-density mass (25 vs. 13%; P=0.06) on the mammogram prior to diagnosis than the 58 'no gain' cases. Our study shows that architectural distortion and non-spiculated high-density masses on the mammogram prior to diagnosis are associated with a possible gain in prognosis. Earlier detection of the carcinomas preceded by these signs may well have an impact on breast cancer mortality and thus warrant extra attention in radiological practice.