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The Salar de Atacama, located in Northern Chile, is a wide salt flat that is characterized by several salt lakes, which are locally called lagunas. The Laguna de la Piedra is one of the salt lake systems that is located in the northernmost sector of the Salar de Atacama. The present paper examines some physicochemical properties of the Laguna de la Piedra as well as the microbial diversity of the evaporite deposits. Under extreme desiccation and ambient UV flux, the evaporite deposits can create favorable endolithic microniches for the development of microorganisms. In the Laguna de la Piedra these deposits host a variety of halophilic microorganisms, which were investigated by using an optical and environmental scanning electron microscope (ESEM) as well as molecular diversity studies based on the small subunit ribosomal (SSU) rRNA of Bacteria, Archaea and Eucarya. We detected a single phylotype of halophilic archaea and a oxytrichid ciliate. Within the bacteria, a variety of Cyanobacteria, Bacteroidetes, Alpha-, Beta- and Deltaproteobacteria, as well as members of the candidate division TM6, were identified.