BACKGROUND: In a prospective study, long term upper-limb morbidity, perceived disabilities in activities of daily life (ADL) and quality of life (QOL) were assessed before and 2 years after sentinel lymph node biopsy (SLNB) or axillary lymph node dissections (ALND) for breast cancer. METHODS: Two hundred and four patients with stage I/II breast cancer, mean age 55.6 years (SD: 11.6) entered the study and 181 patients (89%) could be evaluated after 2 years. Fifty-seven patients underwent SLNB (31%) and 124 patients underwent an ALND (69%). Assessments included pain, shoulder range of motion, muscle strength, arm volume, perceived shoulder disability in ADL and QOL. RESULTS: Significant (P<0.05) changes between before and 2 years after surgery were found in almost all assessments of shoulder function, ADL and several QOL subscales. Patients in the ALND group showed significant more changes in range of motion (ROM), grip strength, arm volume, ADL and QOL physical- and role functioning, pain and sleeplessness and arm symptoms compared to the SLNB group. Multivariate linear regression analysis showed that ALND could predict decrease of ROM, grip strength, ADL and physical functioning (QOL) and increase of arm volume, pain and arm symptoms score (QOL). Radiation on the axilla predicts an additional decrease in shoulder ROM and increase of arm volume. CONCLUSION: Two years after surgery for breast cancer, patients show significantly less treatment related upper limb morbidity, perceived disability in ADL and worsening of QOL after SLNB compared with ALND.