Melphalan is an alkylating agent frequently used in an intravenous formulation to treat hematologic malignancies and solid tumors in both adults and children. According to the manufacturer, melphalan is stable in sterile 0.9% sodium chloride for 90 min at room temperature (RT). Several authors have studied the stability of different concentrations of melphalan; however, most were not adapted to the current manufacturing process applied in pharmaceutical centralized units. This study was conducted to determine the stability of melphalan in 0.9% sodium chloride solutions at concentrations used for intravenous injection in practice. Melphalan is commonly prepared in diluted solutions ranging from 2 to 4 mg/ml for the treatment of adult patients and at lower concentrations (down to 0.5 mg/ml) for pediatric use. Accordingly, these were the three concentrations chosen for this study. Melphalan concentrations were measured with high-performance thin-layer chromatography (HPTLC). At RT, admixtures prepared at 4 mg/ml were stable for up to 8 h without protection from light; however, at lower concentrations, such as 0.5 and 2 mg/ml, stability did not exceed 2 h. When refrigerated, melphalan was stable for 24 h at 2 mg/ml; however, at 0.5 and 4 mg/ml, the drug was not stable. Melphalan solutions present with limited stability at 0.5, 2, and 4 mg/ml and are not adapted for delayed administration in pharmaceutical centralized units. However, at 4 mg/ml and at RT, a stability of 8 h is very interesting in practice and allows sufficient time for preparation, pharmaceutical control, transport, and administration.