Laser irradiation of lichen thalli on heritage stones serves for the control of epilithic and endolithic biological colonizations. In this work we investigate rock samples from two quarries traditionally used as source of monumental stone, sandstone from Valonsadero (Soria, Spain) and granite from Alpedrete (Madrid, Spain), in order to find conditions for efficient laser removal of lichen thalli that ensure preservation of the lithic substrate. The samples presented superficial areas colonized by different types of crustose lichens, i.e. Candelariella vitellina, Aspi cilia viridescens, Rhizocarpon disporum and Protoparmeliopsis muralis in Valonsadero samples and P. cf. bolcana and A. cf. contorta in Alpedrete samples. A comparative laser cleaning study was carried out on the mentioned samples with ns Q-switched Nd:YAG laser pulses of 1064 nm (fundamental radiation), 355 nm (3rd harmonic) and 266 nm (4th harmonic) and sequences of IR-UV pulses. A number of techniques such as UV-Vis absorption spectroscopy, stereomicroscopy, scanning electron microscopy (SEM) at low vacuum, SEM with backscattered electron imaging (SEM-BSE), electron dispersive spectroscopy (EDS) and FT-Raman spectroscopy were employed to determine the best laser irradiation conditions and to detect possible structural, morphological and chemical changes on the irradiated surfaces. The results show that the laser treatment does not lead to the complete removal of the studied lichen thalli, although clearly induces substantial damage, in the form of loss of the lichen upper cortex and damage to the algal layer. In the medium term these alterations could result in the destruction of the lichen thalli, thus providing a degree of control of the biodeterioration processes of the lithic substrate and reducing the chances of subsequent lichen recolonization. (C) 2016 Elsevier B.V. All rights reserved.