Lapatinib (GW 572016) is an oral inhibitor of the tyrosine kinase activity of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2), which are both frequently altered in human malignant tumors. Being a multitargeting agent, it has the theoretical ability to provide more efficient antitumor activity and delay the onset of tumor resistance. Based on promising preclinical results, lapatinib is being extensively studied in cancer patients. In Phase I clinical trials, the side effect profile of lapatinib results are favorable, with a few patients experiencing serious toxicity. Phase II studies showed that lapatinib has meaningful clinical activity in the setting of HER2-positive advanced breast cancer patients. Unfortunately, its activity in epidermal growth factor receptor-dominated cancers, such as colorectal cancer or squamous cell carcinoma of the head and neck, is modest. An extensive program is now ongoing in breast cancer patients to establish the correct role of lapatinib in this clinical setting. Studies in breast cancer, as well as in other solid tumors are also collecting a large amount of biological data. Correlative studies will hopefully clarify predictive factors of lapatinib efficacy that can be applied in clinical practice in order to select patients for treatment.