The 44-year-old believes his former club should have retained the services of the Argentine because of his prowess in front of goal and will struggle to find a replacement
The 25-year-old sealed a move to Napoli for €37 million [£31.5m] last week and has subsequently been unveiled by president Aurelio De Laurentiis on Monday.
However, Mijatovic - who enjoyed a three-year stay in the Spanish capital with los Blancos - is convinced the club's hierarchy will struggle to find someone to replicate the Argentine's goalscoring feats.
The former striker told Cadena COPE: "When Real Madrid purchased Higuain he was seen as a kid with great talent. He was settled in Spain and did well in Spanish football.
"He was key to winning the league title under [Fabio] Capello and has grown a lot at Madrid.
"It is not easy to find a player that scores 25-30 goals a season."
The Argentina international, along with goalkeeper Pepe Reina, were presented to supporters for the first time since their respective moves to Stadio San Paolo before the 3-1 victory over Galatasaray on Monday.
The duo sported the club's colours as they were paraded around the field prior to kick-off but, having failed to obtain international clearance in time for the visit of the Turkish champions, were forced to watch on from the stands as Goran Pandev, Juan Camilo Zuniga and Lorenzo Insigne all scored to secure the win.
Pandev put the hosts ahead in the first-half after guiding his header beyond the Galatasaray stopper.
Nordin Amrabat restored parity for the visitors early in the second-half before Zuniga - who was initially booed by the Partenopei fans amid speculation he is set to join Juventus next summer - and Insigne put the result beyond doubt late on.
Both clubs will now turn their attentions towards London as they travel to the English capital to clash with Arsenal in the Emirates Cup in August.