We analyze the influence of hearth location and smoke dispersal on potential activity areas at Lower Paleolithic Lazaret Cave, France, focusing on archaeostratigraphic unit UA25, where a single hearth was unearthed, and GIS and activity area analysis were performed by the excavators. We simulated smoke dispersal from 16 hypothetical hearth locations and analyzed their effect on potential working spaces. Four activity zones were defined, according to the average smoke exposure recommendations from the World Health Organization (WHO) and Environmental Protection Agency (EPA). We found that the size of the low smoke density area and its distance from the hearth are the main parameters for choosing hearth location. The simulation results show an optimal hearth location zone of about 5 × 5m2, and it is precisely in this zone that the Lower Paleolithic humans of Lazaret Cave placed their hearth. We demonstrate that the optimal hearth location zone correlates not only with the archaeological hearth in UA25 but also with the locations of hearths in other layers. In addition, our smoke density analysis confirmed the detailed GIS and activity area reconstruction conducted by the excavators, strongly reinforcing their interpretation regarding the spatial organization of human behavior at Lazaret Cave.