The influence of tissue compression and external thermal modulation on passive detection of breast tumors using medical microwave radiometry was investigated using multi-physics numerical modeling. A three-dimensional numerical model of the pendant breast with 10 and 6 mm diameter tumors at varying depths (15 mm, 30 mm) was analyzed at thermodynamic equilibrium using a circular waveguide as the receive antenna. The contrast in the brightness temperature, ΔT B , between the unhealthy and healthy breasts was found to be significantly more for breast compression alone, compared to thermal modulation of the tissue surface, irrespective of tissue composition, tumor size, and depth. The study also concludes that small deep-seated tumor with very low metabolic activity that is not detectable by a radiometer with 0.1 °C sensitivity could be detected under breast compression and short duration cold stress. Thus, detection of deep-seated breast tumors can be significantly improved under controlled tissue compression with an optional cold stress. Bioelectromagnetics. © 2019 Bioelectromagnetics Society. © 2019 Bioelectromagnetics Society.