Diagnostic tests, based on nucleic acid extracts from formalin-fixed and paraffin-embedded tissues, are now becoming increasingly common due to the introduction of biological agents for cancer therapy. Unfortunately, the formalin-fixed and paraffin-embedded tissues are heterogeneous in terms of processing and tissue type, and this has an impact on downstream molecular techniques, especially RNA-based techniques. The present review deals with most of the variables connected to the extraction of nucleic acids from formalin-fixed paraffin-embedded tissues, ranging from tissue processing to quality control of extracts. The most recent peer-reviewed publications (mostly published in the past 5 years) and information provided by company websites have been analyzed to compile this review.