Human tumour immunology is at a standstill whereas implemented cancer vaccines have shown effectiveness in inducing immune responses detectable in circulating lymphocytes. In most circumstances, however, such immune responses are not sufficient to induce cancer regression. This paradoxical observation could be explained in several ways depending upon the immunological endpoint used for immune monitoring. For instance, analysis of immune responses in circulating lymphocytes that address the presence of T cells bearing T-cell receptors specific for the epitope used for vaccination, can accurately enumerate the number of T cells elicited by the vaccines but does not yield information about their functional status. Other monitoring strategies may yield general information about the reactivity of various T cells in response to a relevant stimulus and, therefore, may provide information more relevant to the purpose of the immunisation. Furthermore, the material used to monitor immune responses may, in itself, determine the significance of the findings obtained. In the assessment of the therapeutic efficacy of specific cancer treatment, analysis of immune responses in circulating lymphocytes (systemic response) may not be as relevant as the analysis of the same effector populations within the tumour microenvironment (peripheral response). This review will describe a novel approach that allows extreme flexibility in the analysis of systemic and peripheral responses by accurately measuring the level of expression of relevant genes using quantitative real-time reverse transcriptase polymerase chain reaction.