Skin-based samples (leather, skin, and parchment) in archaeological, historic and museum settings are among the most challenging materials to radiocarbon (14C) date in terms of removing exogenous carbon sources—comparable to bone collagen in many respects but with much less empirical study to guide pretreatment approaches. In the case of leather, the 14C content of materials used in manufacturing the leather can vary greatly. The presence of leather manufacturing chemicals before pretreatment and their absence afterward is difficult to demonstrate, and the accuracy of dates depends upon isolating the original animal proteins and removing exogenous carbon. Parchments differ in production technique from leather but include similar unknowns. It is not clear that lessons learned in the treatment of one are always salient for treating the other. We measured the 14C content of variously pretreated leather, parchment, skin samples, and extracts, producing apparent ages that varied by hundreds or occasionally thousands of years depending upon sample pretreatment. Fourier Transform Infrared Spectroscopy (FTIR) and C:N ratios provided insight into the chemical composition of carbon reservoirs contributing to age differences. The results of these analyses demonstrated that XAD column chromatography resulted in the most accurate 14C dates for leather and samples of unknown tannage, and FTIR allowed for the detection of contamination that might have otherwise been overlooked.