We aim to investigate the incidence, patterns and timing of brain metastases in advanced breast cancer patients who have previously received trastuzumab. Eighty-seven patients who had received trastuzumab for advanced breast cancer from November 1999 to September 2003 at the Royal Marsden Hospital were assessed. With a median follow-up period of 11 months from commencing trastuzumab, 23 patients developed brain metastases (30% at 1 year; 95% CI 58-82%). Among 57 patients who had clinical benefits on trastuzumab, 12 (21%) patients developed first disease progression in brain with 75% of them had isolated CNS progression. Moreover, among patients who received trastuzumab as first line treatment, isolated brain metastases were the initial site of progression in 17% patients. Nearly all patients developed parenchymal brain disease. This study shows brain metastases are common phenomenon in HER2 positive advanced breast cancer patients receiving trastuzumab and also may implicate the brain as a sanctuary site for early relapse in this patient cohort.