In the last few years, many targeted agents have been introduced for the treatment of advanced and/or metastatic renal cell carcinoma. Such agents have demonstrated a prolongation of progression-free survival, but the optimal treatment strategy is still unclear. Many decisions of clinicians are based on pivotal trial results that are not always transferable to a real-world setting. We report a retrospective monoinstitutional experience of first-line treatment with pazopanib in a series of patients with metastatic renal cell carcinoma. The aim of the present experience was to evaluate the activity and safety of pazopanib in an unselected patient population extracted from clinical practice. Our findings suggest that efficacy and toxicity profiles of pazopanib in the real-world population appear consistent with trial-based expectations. The preliminary results need to be confirmed on a larger cohort, due to the small number of patients evaluated.