Loss of surface expression of class I major histocompatibility antigens is commonly observed in malignant tumors and has been considered one of the mechanisms for escape from cytotoxic T cells. However, natural killer cells kill cells lacking HLA class I antigens. In the present study, we characterized by immunohistochemistry the HLA class I expression of breast carcinomas from 187 patients with TNM stages I and II, diagnosed 1981-1984, using beta(2)-microglobulin as a marker and evaluated the effect on survival with a follow-up of up to 14 years. The largest group (48%) consisted of HLA class I-negative tumors (< or =10% of cells stained), mixed expression (>10% and <80% of cells stained) was seen in 36% and only 15% were classified as HLA class I-positive (> or=80% cells stained). No associations could be established with various clinicopathological parameters, such as tumor size, presence of lymph node metastases, histological grade, expression of hormone receptors, S phase and p53 mutations. There was no effect on recurrence-free survival in the whole group; but among node-negative patients (n = 86), those who had tumors with mixed HLA class I expression had a significantly higher probability of disease recurrence (OR = 3.42, p = 0.014) than patients with either HLA class I-positive or -negative tumors, particularly after more than 5 years. In node-positive patients who received adjuvant therapy, this phenotype was not associated with disease recurrence.