Different lead sources were identified in a large uranium tailings deposit (5Mton) in the Central Region of Portugal using lead isotopic ratios obtained by ICP-QMS. These ratios helped to clarify the different sources of Pb within the tailings deposit and the impact of the tailings on the surroundings. Ten depth profiles were used for isotopic characterization of the tailings deposit; the lead background signature was evaluated in seven regional rocks (granites) and was defined as being 28 ± 1 mg kg−1 for Pb bulk concentration and with isotopic ratios of 1.264(2) for 206Pb/207Pb and 1.962(7) for 208Pb/206Pb. In order to understand Pb isotope distribution within the tailings deposit, simple mixing/mass balance models were used to fit experimental data, involving: (1) the background component; (2) uranium ores (pitchblende) characterized by the ratios 206Pb/207Pb of 1.914(3) and 208Pb/206Pb of 1.235(2); and (3) an unknown Pb source (named ‘Fonte 5’) characterized by the ratios 206Pb/207Pb of 3.079(7) and 208Pb/206Pb of 0.715(1). This unknown source showed high radiogenic ratios found in the water of some tailings depth profiles located in a very specific position in the dump. In terms of isotopic characterization, 69% of the deposit material resulted from the background source, 25% from uranium minerals and only 6% from other uranium mines in the region. Finally, the environment impact revealed that the pollution was focused only in the beginning of the stream and not in the surroundings, nor in the groundwater system. The lead in the water was found only in colloidal form with a clear pitchblende signature. Those data revealed possible remobilization phenomena along the bedside and margins of the watercourse.