The first observation of top quark production in proton-nucleus collisions is reported using proton-lead data collected by the CMS experiment at the CERN LHC at a nucleon-nucleon center-of-mass energy of 8.16 TeV. The measurement is performed using events with exactly one isolated electron or muon and at least four jets. The significance of the ttbar signal against the background-only hypothesis is above five standard deviations. The measured cross section is 45±8 nb, consistent with predictions from perturbative quantum chromodynamics. We will discuss the experimental and theoretical aspects of this measurement including the potential probing of the time structure of the Quark Gluon Plasma with an analogous measurement in nucleus-nucleus collisions.