A method has been developed to study the content of anthocyanidins, proanthocyanidicins, and anthocyanins in wine lees, an abundant byproduct from wineries. Detection/quantitation of the target compounds was carried out by a hyphenated system consisting of a solid-phase extraction workstation (Prospekt-2 unit) online coupled to a liquid chromatograph-triple-quadrupole tandem mass spectrometer (LC-MS/MS), where standards were used for identification/quantitation of both anthocyanidins and proanthocyanidins. Owing to the lack of anthocyanins standards, advantages from the use of data-dependent methods were taken for their identification and confirmatory analysis. Combination of the scanning methods (viz. product-ion, precursor-ion, and neutral-loss scanning) allowed identifying five different anthocyanins present in wine residues. The results thus obtained have been validated by complementary analysis of the extracts using LC-TOF/MS in high-resolution mode. Quantitation of the monitored compounds was supported on selected reaction monitoring (SRM) and calibration curves run with standards of anthocyanidins and proanthocyanidins.