Demineralization is a rapidly growing and challenging aspect of various scientific disciplines such as astrobiology, paleoclimatology, geomedicine, archaeology, geobiology, dentistry, histology, biotechnology, and others to mention just a few. Biomineralized structures and tissues are composites, containing a biologically produced organic matrix and nano-or microscale amorphous or crystalline minerals. In humans, head and neck is a complex structure of both soft and hard tissues. Soft tissues put forth little resistance to the histochemical techniques but lesions affecting hard tissues need intricate, technique sensitive methodology for interpretation and diagnosis. The choice of decalcifier is influenced by four interdependent factors: urgency of the case, degree of mineralization, extent of investigation and staining techniques required. So, an ideal decalcifying agent should ensure complete removal of calcium, cause minimum damage to cells and tissues, cause non-impairment to subsequent staining and decalcify at reasonable speed.