Methods of directly isolating nucleic acid from an embedded biological sample are provided. An emulsified digest is generated in the presence of a thermostable protease, and an additive selected from an alkylene glycol, a poly(alkylene glycol), or a block copolymer having an average Mn of 76 to 2900, or a salt or derivative or combination thereof. Nucleic acid is isolated directly from the emulsified digest. The methods eliminate the use of organic solvents such as xylene in a deparaffinization step prior to isolating nucleic acids from paraffin-embedded samples, for example.