In case of clinical analysis, especially in blood lead (Pb-B) and cadmium (Cd-B) determination, the accuracy and precision of the method are crucial. The objective of this article is to present a simple and useful method for Pb-B and Cd-B determination using ICP-MS (inductively coupled plasma-mass spectrometry) as well as GF-AAS (graphite furnace-atomic absorption spectrometry). The principle of the method is based on the deproteinization of blood samples by addition of 5% nitric acid that eliminates the presence of the protein in the samples, thereby excluding the influence of the organic matrix on the result determinations. A comparison of the two techniques ICP-MS and GF-AAS was established for Pb and Cd determinations in the same 40 blood samples collected from lead workers. The results showed that validation parameters for ICP-MS and GF-AAS were similar, however better for ICP-MS for Pb-B determinations. The detection limit (3×SD) for Pb-B determinations for ICP-MS and GF-AAS was, respectively, 0.16 and 1.0 μg/l, and for Cd-B it was, respectively, 0.08 and 0.02 μg/l. Correlation coefficients (rs) for comparable Pb-B and Cd-B determinations, using these two techniques, showed very good statistically significant correlations and were r = 0.9988, P < 0.0001 for Pb-B and r = 0.9949, P < 0.0001 for Cd-B. The obtained results indicate that the method of deproteinization of blood samples is still the best way to eliminate spectral interferences and influence of the organic matter. The elaborated method is especially dedicated to clinical laboratories and determined low concentrations of lead and cadmium in biological samples.