Our previous studies revealed that leukocyte infiltration could trigger breast and prostate tumor invasion through physical disruption of tumor capsules. Our current study, involving multiple types of human tumors, further suggests that leukocyte infiltration also triggers metastasis through the following pathways : 1) the physical movement into the epithelium disrupts inter-cellular junctions and surface adhesion molecules, which cause the disassociation of tumor cells from tumor cores, 2) some of these tumor cells subsequently form tight junctions with the plasma membranes of leukocytes creating tumor cell-leukocyte chimeras (TLCs), and 3) the leukocytes of TLCs impart migratory capacity to associated tumor cell partners. Our findings suggest a novel pathway for tumor cell dissemination from primary sites and journey to new sites.