Description: Background: Most of the blood tests aiming for breast cancer screening rely on quantification of a single or few biomarkers. The aim of this study was to evaluate the feasibility of detecting breast cancer by analyzing the total biochemical composition of plasma as well as peripheral blood mononuclear cells (PBMCs) using infrared spectroscopy. Methods: Blood was collected from 29 patients with confirmed breast cancer and 30 controls with benign or no breast tumors, undergoing screening for breast cancer. PBMCs and plasma were isolated and dried on a zinc selenide slide and measured under a Fourier transform infrared (FTIR) microscope to obtain their infrared absorption spectra. Differences in the spectra of PBMCs and plasma between the groups were analyzed as well as the specific influence of the relevant pathological characteristics of the cancer patients. Results: Several bands in the FTIR spectra of both blood components significantly distinguished patients with and without cancer. Employing feature extraction with quadratic discriminant analysis, a sensitivity of ~90 % and a specificity of ~80 % for breast cancer detection was achieved. These results were confirmed by Monte Carlo cross-validation. Further analysis of the cancer group revealed an influence of several clinical parameters, such as the involvement of lymph nodes, on the infrared spectra, with each blood component affected by different parameters. Conclusion: The present preliminary study suggests that FTIR spectroscopy of PBMCs and plasma is a potentially feasible and efficient tool for the early detection of breast neoplasms. An important application of our study is the distinction between benign lesions (considered as part of the non-cancer group) and malignant tumors thus reducing false positive results at screening. Furthermore, the correlation of specific spectral changes with clinical parameters of cancer patients indicates for possible contribution to diagnosis and prognosis.