Purpose:Monte Carlo studies of gold nanoparticle (GNP) dose enhancement on macroscopic scales in radiotherapy have modeled GNPs in tissue as a homogeneous mixture of gold and tissue. Using an explicit model of GNPs randomly positioned in a small volume (1 µm3) of tissue, this study aims to quantify the dose to the biologically relevant component of a goldtissue mixture, enabling a conversion from macroscopically‐scored dose.Methods:Using the PENELOPE Monte Carlo code with the penEasy package, we modeled a 1 µm3 volume containing either a tissue‐gold mixture or GNPs suspended in ICRU 4‐component tissue at various gold concentrations (0, 5, 10, and 15 mg Au/g tissue) and GNP diameters (20, 30, 40, 50 nm). The volume was irradiated with monoenergetic photon and electron beams, ranging from 110 eV to 6 MeV. Interaction forcing was utilized to increase simulation efficiency. Energy deposition was scored in the tissue for each case and was converted to dose. For each scenario, we calculated a conversion factor, the ratio of dose‐to‐tissue to dose‐to‐mixture as a function of energy.Results:The conversion factor was plotted as a function of energy for both photons and electrons. For electrons, the conversion factor was relatively unaffected by any of the parameters, including energy, ranging between 0.98–1.02. For photons, the factor was very energy dependent, with a range of 0.49–1.02. The factor was lowest for 10–100 keV photons. The conversion factor generally decreased with increasing GNP concentration and increasing GNP size.Conclusion:With a large variation in the conversion factor with incident energy, dose deposition is dependent on the spectrum incident on a volume. By scoring the energy spectrum in a given volume, one can provide a scenario‐specific conversion factor, allowing fast, detailed Monte Carlo simulations without the need for explicit GNP‐definition.