Node-negative breast cancer patients have a relatively good prognosis, but eventually one-third will die of the disease. Thus, prognostic factors to identify the high-risk group among these patients are needed. We retrospectively determined the Mitotic Activity Index (MAI) for a large series of node-negative breast cancer patients (n= 468) with tumours smaller than 5 cm, who only received locoregional treatment. Patients were followed for up to 29 years; crude and relative survival were calculated, both univariate and multivariate. Relative survival differed significantly according to MAI (p= 0.05), the difference occurred in the first 5 years after diagnosis and remained constant thereafter. After adjustment, MAI still significantly affected relative survival (RER, 1.9; 95% CI, 1.1–3.5). Tumour size also increased the risk, but this was not statistically significant (RER, 1.5; 95% CI, 0.8–2.7). Survival of patients with a T1 tumour and MAI < 10 was similar to that for the general population in the first 5 years after diagnosis. In conclusion, MAI significantly predicted long-term survival for T1/T2N0 breast cancer. Adjuvant systemic therapy appears to have little benefit for node-negative breast cancer patients with a T1 tumour, regardless of the MAI. For those with a T2 tumour and a MAI ≥ 10 systemic therapy might have reduced mortality. The need for close surveillance of node-negative breast cancer patients with a T1 tumour and MAI <10 seems limited.