Breast cancer is the most prevalent form of cancer in women with over 266,000 new cases diagnosed every year in the United States. The various methods used for breast cancer screening range in accuracy and cost; however, there is no easily reproducible, reliable, low-cost, nonradiative screening modality currently available, especially for dense breast tissue. Steady-state infrared imaging (IRI) is promising in this area as it is unaffected by tissue density and has the potential to detect tumors by measuring and capturing the thermal profile on the breast surface induced by increased blood perfusion and metabolic activity associated with the tumor. In our proposed clinical IRI and simulation approach (CIRIS™), women with biopsy-proven breast cancer are imaged with IRI in the prone position. The prone position is able to provide a thermal profile of the entire breast without any gravitational deformation or thermal abnormalities in the inframammary fold. A digital model, created using clinical images, is thermally simulated through a commercially available software using known tumor characteristics obtained from the available magnetic resonance imaging (MRI) data. The resulting surface thermal profile is compared with the IRI images. In the three cases discussed here, the digital model was able to accurately predict the breast surface temperature distribution, showing the promise of this approach in breast cancer screening. This preliminary work is expected to lead the way for a larger clinical study in the future to establish IRI as an adjunctive screening technique.