Method and instrument for analysing a tissue sample. Localized concentrations of an analyte are measured at a plurality of spaced apart locations around a controlled depth. Spatial variance of the analyte is calculated based on the measured analyte concentrations. The procedure is repeated while varying the controlled depth to obtain the spatial variance as a function of depth. Tissue at a particular depth may be evaluated as tumour tissue when the spatial variance is below the threshold. For example, a section distance is calculated between the tissue surface and a depth where the measured spatial variance crosses a predetermined threshold variance. Feedback can be provided based on a comparison between a calculated section distance and a pre-set minimum section margin.