The aim of this study was to determine whether the excess risk of axillary lymph node metastases (N+) differs between interval breast cancers arising shortly after a negative mammography and those presenting later. In a registry-based series of pT1a-pT3 breast carcinoma patients aged 50-74 years from the Italian screening programmes, the odds ratio (OR) for interval cancers (n=791) versus the screen-detected (SD) cancers (n=1211) having N+ was modelled using forward stepwise logistic regression analysis. The interscreening interval was divided into 1-12, 13-18, and 19-24 months. The prevalence of N+ was 28% among SD cancers. With a prevalence of 38%, 42%, and 44%, the adjusted (demographics and N staging technique) OR of N+ for cancers diagnosed between 1-12, 13-18, and 19-24 months of interval was 1.41 (95% confidence interval 1.06-1.87), 1.74 (1.31-2.31), and 1.91 (1.43-2.54), respectively. Histologic type, tumour grade, and tumour size were entered in turn into the model. Histologic type had modest effects. With adjustment for tumour grade, the ORs decreased to 1.23 (0.92-1.65), 1.58 (1.18-2.12), and 1.73 (1.29-2.32). Adjusting for tumour size decreased the ORs to 0.95 (0.70-1.29), 1.34 (0.99-1.81), and 1.37 (1.01-1.85). The strength of confounding by tumour size suggested that the excess risk of N+ for first-year interval cancers reflected only their higher chronological age, whereas the increased aggressiveness of second-year interval cancers was partly accounted for by intrinsic biological attributes.