The selection of patients with axillary lymph node-negative breast cancer who should receive adjuvant therapy today is confused by an expanding arsenal of putative prognostic factors. The size of the primary tumor remains the dominant factor in sorting among this group of patients, with general agreement that tumors 1 cm or less should be spared adjuvant systemic therapy outside of a clinical trial. There are a few favorable histologic subgroups that may be added to this excluded group: ductal carcinoma in sitn and pure tubular, papillary, and typical medullary tumors. For the larger tumor (generally > 2 cm in diameter, but always > 3 cm), there is little disagreement that adjuvant therapy is indicated. The host of additional prognostic factors are directed mainly toward the group of tumors that fall between these two categories. Nuclear grade, S-phase, and perhaps p53 mutations influence decisions for treatment by their elevation. Although the decision remains with the patient and the recommendation with the mature judgment of the clinician, the prognostic indicators available continue to multiply. That an indicator can retrospectively sort prognosis is of limited interest. It requires prospective validation in another patient population, reproducibility in other laboratories, and multivariate analysis among factors measured on the same population of patients to integrate a factor into clinical decision-making. It is only beginning to be accomplished. The next generation of factors being sought are those that predict for response or lack of response to specific therapies, rather than merely indicating natural history. Estrogen and progesterone receptors are the prototypes of this class of indicators.