Lysosomes and lysosomal enzymes are known to be involved in cancer processes. However, integrated biochemical and cell biology studies are necessary to understand how lysosomal enzymes could initiate cancer. Most breast cancer is initiated in the milk ducts. The hypothesis presented here is that lysosomal enzymes are exocytosed into the milk ducts where these hydrolytic enzymes damage cells leading to the initiation of cancer. Lysosomal enzymes include: many cathepsins, acid phosphatases, DNAases, ribonucleases, sulfatases, glucuronidase, lipases, neuramidase, lysozyme, fucosidase, phosphodiesterases, glucosidases, galactosidases, mannosidase, and glucosaminidase. Risk factors for breast cancer that could initiate activity of lysosomal enzymes include: ionizing radiation, oxidative stress, estrogen, environmental toxicants and dietary components. Measurements of multiple lysosomal enzyme activities and their biochemical pathways are vital to the understanding of protectors to inhibit lysosomal enzyme activities that might be leading to breast cancer. Non-invasive screening assays could be developed to measure in vivo milk duct lysosomal enzyme activities. Lysosomal enzyme activities may be precursors to the onset of other kinds of cancer with other similar non-invasive screening techniques possible.