Relationships between membrane E-cadherin reactivity of invasive carcinoma, a dyshesive growth pattern, and lobular carcinoma–type systemic metastases were studied in 295 breast carcinomas and 57 patients with lobular carcinoma systemic metastases. There were 143 pure lobular carcinomas, 80 mixed (lobular and ductal) carcinomas, and 72 pure ductal carcinomas. Two (7%) of 30 mixed, predominantly lobular carcinomas, 23 (61%) of 38 mixed carcinomas, and 8 (67%) of 12 mixed, predominantly ductal carcinomas had E-cadherin staining in more than 10% of the lobular carcinoma cells. Lobular carcinoma–type systemic metastases were identified in 45 cases (38 [84%], pure lobular; 5 [11%], mixed; 2 [4%], pure ductal). No E-cadherin staining was found in 42 (98%) of 43 lobular carcinomas in cases of lobular carcinoma–type systemic metastases and all 57 cases of lobular carcinoma systemic metastases. Absent cell-to-cell adhesion seems to be a necessary property of carcinoma cells to facilitate permeation through tissue planes and produce characteristic lobular carcinoma–type systemic metastases. The level of decreased E-cadherin expression at which a dyshesive growth pattern emerges in primary breast carcinomas may be less than the level associated with lobular carcinoma–type systemic metastases.