Knowledge on lichen and microbial colonization as well as associated biodeterioration processes of the stone cultural heritage is needed to establish proper conservation programs, but is still poor for stonework in semi-arid regions. In this study, lichen diversity was characterized on seven monumental buildings of the Pasargadae UNESCO-world heritage site (Iran). The risk of biodeterioration processes associated to lichen occurrence on two types of limestones, and the lichen resilience to mechanical cleaning intervention were examined. Physico-chemical substrate features and climatic conditions, combined with the agricultural surrounding and tourist disturbance, supported a pervasive colonization by species-poor epi- and endolithic communities, and fast recolonization processes by nitrophytic species after mechanical removal. The endolithic growth of some lichens and the penetration of hyphal structures of epilithic ones, examined by light and electron microscopy, were associated to stone disintegration and dissolution at the lichen-rock interface. Endolithic cyanobacteria were detected under lichen thalli, likely contributing to deterioration processes. Colonization and deterioration patterns did not appear peculiar with respect to previous investigations on similar communities in different climatic regions, and were mostly related to the different examined lithologies, indicating lichens as harmful biodeteriogens of the sedimentary rock materials used in the stone cultural heritage of semi-arid regions.