Four simple methods are evaluated to determine their accuracies for establishing the interface location in secondary ion mass spectrometry intensity depth profiles of organic layers where matrix effects have not been measured. Accurate location requires the separate measurement of each ion's matrix factor. This is often not possible, and so estimates using matrix‐less methods are required. Six pure organic material interfaces are measured using many secondary ions to compare their locations from the four methods with those from full evaluation with matrix terms. For different secondary ions, matrix effects cause the apparent interface positions to vary over 20 nm. The shifts in the intensity profiles on going from a layer of P into a layer of Q are in the opposite direction to that for going from Q into P, so doubling layer thickness errors. The four methods are as follows: M1, use of the median interface position in the intensity profiles for the five lightest ions for 15 ≤ m/z ≤ 150; M2, extrapolation of the position for each ion to m/z = 0 for ions with m/z ≤ 150; M3, as M2 but for m/z ≤ 300; and M4, the extreme positions for all m/z ≤ 100. Comparison with the location using matrix terms shows their ranking, from best to worst, to be M4, M3, M1, and M2 with average errors of 10%, 12%, 14%, and 17%, respectively, of the profile interface full widths at half maximum. Use of pseudo‐molecular ions is very much poorer, exceeding 50%, and should be avoided.