ABSTRACT Millisecond pulsars in timing arrays can act as probes for gravitational wave detection and improving the Solar system ephemerides among several other applications. However, the stability of the integrated pulse profiles can limit the precision of the ephemeris parameters and in turn the applications derived from it. It is thus crucial for the pulsars in the array to have stable integrated pulse profiles. Here we present evidence for long-term profile instability in PSR J1022+1001 which is currently included in the European and Parkes pulsar timing arrays. We apply a new evaluation method to an expanded data set ranging from the Effelsberg Pulsar Observing System backend used in the 1990s to that of data from the current PSRIX backend at the Effelsberg Radio Telescope. We show that this intrinsic variability in the pulse shape persists over time-scales of years. We investigate if systematic instrumental effects like polarization calibration or signal propagation effects in the interstellar medium causes the observed profile instability. We find that the total variation cannot be fully accounted for by instrumental and propagation effects. This suggests additional intrinsic effects as the origin for the variation. We finally discuss several factors that could lead to the observed behaviour and comment on the consequent implications.