Various parameters can introduce uncertainties in the lung activity measurements of actinides. In this study, uncertainties due to non-uniform distribution of activity in the lungs are evaluated. To study the effect of nonuniform distribution, lungs of ICRP male thorax voxel and resized phantoms are divided into upper and lower parts of both right and left lungs as well as into anterior and posterior lung regions. Simulation of uniform and non-uniform distribution of activity in lungs is carried out using thorax voxel phantoms in FLUKA for Phoswich and an array of three HPGe detectors for 18–238 keV photons. Source sampling for non-uniform distribution of activity is carried out by selecting the source points by varying the weightage to 0.4, 0.5, 0.6 and 1 in different parts of lungs. Uncertainties in lung activity estimation at different energies are quantified in the form of scattering factors (SFs) which are geometric standard deviations. The SFs due to non-uniform distribution of activity of the order of 0.4–0.6 in different parts of the lungs are found to be ~ 1.25 for Phoswich and HPGe array detectors above 18 keV.