Paper spray mass spectrometry (PS-MS) is explored as a fast and convenient way for direct analysis of molecules in tissues with minimum sample pretreatment. This technique allows direct detection of different types of compounds such as hormones, lipids, and therapeutic drugs in short total analysis times (less than 1 min) using a small volume of tissue sample (typically 1 mm(3) or less). The tissue sample could be obtained by needle aspiration biopsy, by punch biopsy, or by rubbing a thin tissue section across the paper. There exists potential for the application of paper spray mass spectrometry together with tissue biopsy for clinical diagnostics.