Summary Surgeons have long been concerned that cancer may be disseminated by shedding of tumour cells into the bloodstream during surgery. Early claims that cancer operations induced an increase in the number of tumour cells shed into the circulation were subsequently discredited, and the issue has remained unresolved. We used immunocytochemistry for cytokeratins to detect tumour cells in effluent blood from breast carcinomas in 18 patients undergoing surgery. Tumour cells were detectable in 6/18 patients during surgery, in only one patient before operation and in none post-operatively (P = 0.025). Circulating cells were associated with vascular invasion within the primary tumour (P = 0.032). No cytokeratin-positive cells were found in blood from ten normal volunteers or four patients undergoing surgery for other breast conditions. These results confirm that cancer surgery in humans results in an increase in the shedding of tumour cells into the circulation. The implications for prognosis and practice should be determined by larger prospective studies.Keywords: circulating cell; metastasis; surgery Blood-borne metastasis is the greatest obstacle to cure in patients with cancer. Metastasis is a complex process by which tumour cells enter blood vessels, circulate and exit the system at distant sites (Hart and Saini, 1992). Trauma to tumours increases both cell shedding and metastasis in animal models (Tyzzer, 1913;Liotta et al., 1976), leading to concern that cancer surgery might have similar effects in humans. Early studies of cell shedding in humans were confounded by major sampling and cell identification errors, and a general appreciation of the inadequacy of contemporary techniques led to a decline in interest in the subject (Salsbury, 1975). In recent years emphasis in metastasis research has shifted to the phenotype of the cancer cell, and a number of enzymatic and adhesion molecules have been implicated in the metastatic process (Fidler, 1991;Hart and Saini, 1992). The importance of the extent of tumour cell shedding into the bloodstream, and the effects of this on cancer surgery have, by contrast, been neglected. The significance of these factors in determining outcome therefore remains unknown.Monoclonal antibodies against epithelial-restricted epitopes now permit reliable identification of small numbers of carcinoma cells among large numbers of cells of haemopoetic lineage in the bloodstream and bone marrow (Leather et al., 1993;Pantel et al., 1993